This document summarizes a computational fluid dynamics simulation that studied the effects of nanoparticle size on the temporal and spatial concentration profiles of nanoparticles delivered to the brain and brain tumor for drug delivery purposes. The simulation used a convection-diffusion model to describe nanoparticle transport. It found that smaller nanoparticles reached a steady-state concentration faster with a lower average concentration. Smaller nanoparticles also distributed over a larger volume at steady-state, but with a smaller maximum concentration in the brain and tumor regions.
Berbeco et al, Low Z target switching to increase tumor endothelial cell dose...David Parsons
This study proposes using a linear accelerator with a switchable low Z target to increase the proportion of low energy photons during gold nanoparticle-aided radiation therapy. This is done to enhance the dose delivered to tumor endothelial cells via the photoelectric effect. Monte Carlo simulations show that a carbon target produces a nearly four-fold increase in low energy (<150 keV) photons compared to a standard Cu/W target. This corresponds to a 7.7-fold higher dose enhancement to endothelial cells when gold nanoparticles are present. While the low Z target increases surface dose, this can be mitigated by using multiple beam angles in treatment planning. A prototype switchable target has been built and could allow customizing the photon energy spectrum for each treatment
Numerical Prediction of Microbubble Attachment in Biological Flows (2)Joshua Gosney
This document presents a numerical model to estimate hydrodynamic forces on microbubbles in biological flows. The model is validated by comparing predictions of microbubble attachment to experimental measurements under controlled flow conditions. The model finds stable microbubble attachment can be expected up to average fluid velocities of 0.025 cm/s near the microbubble, corresponding to particle Reynolds numbers around 0.001. Both computational fluid dynamics simulations and simplified analytical models are used to predict forces on microbubbles in capillaries, venules and veins.
This document summarizes a study that evaluated the effect of stimulus intensity on mapping parameters using a novel transcranial magnetic stimulation (TMS) protocol. The study found that:
1) Map volume and area showed a significant positive relationship with increasing stimulus intensity, but mapping parameters were highly reliable within intensities.
2) The center of gravity (CoG) coordinates and map shape were unaffected by intensity changes.
3) These findings validate the novel TMS protocol and suggest it reliably measures cortical excitability while being less time-consuming than conventional methods, making it suitable for clinical use.
MODELING DEHYDRATION OF ORGANIC COMPOUNDS BY MEANS OF POLYMER MEMBRANES WITH ...ceij journal
The present study analyzes the amount of water-alcohol separation by pervaporation and use of polymer membranes with help of Artificial Neural Network and COMSOL Multiphysics. The influence of such parameters as volumetric flow rate, temperature, separation factor and permeate flux over the efficiency of dehydration process was analyzed through Artificial Neural Network. The reserarcher in this study used a Feed Forward multilayer Perceptron neural network with a back propogation algorithm and LevenbergMarquardt function with two inputs and two outputs. The Tansig transfer function was used for the hudden layer and Purelin was used for the output layer; five nerons were defined for the hidden layer. After data precessing, 70 percent of the data was allocated for learning, 15 percent was allocated for validation, and 25 percent was allocated for testing. The output values of Artificial Neural Network modelling were compard with the real values of pervaporation for separation of water from Ethanol, Acetone, and butanol. The results revealed that the proposed model had a good performance. Moreover, the output of COMSOL software for pervaporation of five different alcohols were compared with the real values, and the error percentage of the actual amount of flux was calculated with the modeling value by means of related membranes. The results of COMSOL modeling showed that the error percentages of 3.049, 3.7, 3.51, 2.88, and 3.82 were respectively achieved for dehydration process of Acetone, Butanol, Ethanol, Isopropanol and Methanol
Biologically Effective Equivalent Uniform Dose to compute Tumor Control Proba...tskehwar
The document discusses calculating tumor control probability (TCP) and normal tissue complication probability (NTCP) for intensity-modulated radiation therapy (IMRT) plans using the biologically effective equivalent uniform dose (BEEUD) concept. TCP and NTCP values were calculated for sample IMRT plans using the BEEUD methodology and compared to other methods. The BEEUD concept was able to calculate TCP similarly to voxel-based methods and provides an advantage for pre-treatment plan evaluation, though it may produce different NTCP values than the L-K model.
Tema “Controlling u mojoj kompaniji”.
Autori: Apatinska pivara, Erste bank, Grand casino, Hemofarm, Hichert, IBM, Nelt grupa, NIS, OMV, Porsche SCG, Telenor, Wiener osiguranje
Este artículo discute tres aspectos clave que un tutor en línea debe considerar. Primero, explora los nuevos roles y funciones de un tutor virtual como diseñador de currículos, proveedor de contenido y facilitador del aprendizaje. Segundo, analiza las herramientas de comunicación sincrónicas y asincrónicas que un tutor puede utilizar. Tercero, propone diferentes estrategias pedagógicas que un tutor puede implementar para enseñar a los estudiantes en línea.
Berbeco et al, Low Z target switching to increase tumor endothelial cell dose...David Parsons
This study proposes using a linear accelerator with a switchable low Z target to increase the proportion of low energy photons during gold nanoparticle-aided radiation therapy. This is done to enhance the dose delivered to tumor endothelial cells via the photoelectric effect. Monte Carlo simulations show that a carbon target produces a nearly four-fold increase in low energy (<150 keV) photons compared to a standard Cu/W target. This corresponds to a 7.7-fold higher dose enhancement to endothelial cells when gold nanoparticles are present. While the low Z target increases surface dose, this can be mitigated by using multiple beam angles in treatment planning. A prototype switchable target has been built and could allow customizing the photon energy spectrum for each treatment
Numerical Prediction of Microbubble Attachment in Biological Flows (2)Joshua Gosney
This document presents a numerical model to estimate hydrodynamic forces on microbubbles in biological flows. The model is validated by comparing predictions of microbubble attachment to experimental measurements under controlled flow conditions. The model finds stable microbubble attachment can be expected up to average fluid velocities of 0.025 cm/s near the microbubble, corresponding to particle Reynolds numbers around 0.001. Both computational fluid dynamics simulations and simplified analytical models are used to predict forces on microbubbles in capillaries, venules and veins.
This document summarizes a study that evaluated the effect of stimulus intensity on mapping parameters using a novel transcranial magnetic stimulation (TMS) protocol. The study found that:
1) Map volume and area showed a significant positive relationship with increasing stimulus intensity, but mapping parameters were highly reliable within intensities.
2) The center of gravity (CoG) coordinates and map shape were unaffected by intensity changes.
3) These findings validate the novel TMS protocol and suggest it reliably measures cortical excitability while being less time-consuming than conventional methods, making it suitable for clinical use.
MODELING DEHYDRATION OF ORGANIC COMPOUNDS BY MEANS OF POLYMER MEMBRANES WITH ...ceij journal
The present study analyzes the amount of water-alcohol separation by pervaporation and use of polymer membranes with help of Artificial Neural Network and COMSOL Multiphysics. The influence of such parameters as volumetric flow rate, temperature, separation factor and permeate flux over the efficiency of dehydration process was analyzed through Artificial Neural Network. The reserarcher in this study used a Feed Forward multilayer Perceptron neural network with a back propogation algorithm and LevenbergMarquardt function with two inputs and two outputs. The Tansig transfer function was used for the hudden layer and Purelin was used for the output layer; five nerons were defined for the hidden layer. After data precessing, 70 percent of the data was allocated for learning, 15 percent was allocated for validation, and 25 percent was allocated for testing. The output values of Artificial Neural Network modelling were compard with the real values of pervaporation for separation of water from Ethanol, Acetone, and butanol. The results revealed that the proposed model had a good performance. Moreover, the output of COMSOL software for pervaporation of five different alcohols were compared with the real values, and the error percentage of the actual amount of flux was calculated with the modeling value by means of related membranes. The results of COMSOL modeling showed that the error percentages of 3.049, 3.7, 3.51, 2.88, and 3.82 were respectively achieved for dehydration process of Acetone, Butanol, Ethanol, Isopropanol and Methanol
Biologically Effective Equivalent Uniform Dose to compute Tumor Control Proba...tskehwar
The document discusses calculating tumor control probability (TCP) and normal tissue complication probability (NTCP) for intensity-modulated radiation therapy (IMRT) plans using the biologically effective equivalent uniform dose (BEEUD) concept. TCP and NTCP values were calculated for sample IMRT plans using the BEEUD methodology and compared to other methods. The BEEUD concept was able to calculate TCP similarly to voxel-based methods and provides an advantage for pre-treatment plan evaluation, though it may produce different NTCP values than the L-K model.
Tema “Controlling u mojoj kompaniji”.
Autori: Apatinska pivara, Erste bank, Grand casino, Hemofarm, Hichert, IBM, Nelt grupa, NIS, OMV, Porsche SCG, Telenor, Wiener osiguranje
Este artículo discute tres aspectos clave que un tutor en línea debe considerar. Primero, explora los nuevos roles y funciones de un tutor virtual como diseñador de currículos, proveedor de contenido y facilitador del aprendizaje. Segundo, analiza las herramientas de comunicación sincrónicas y asincrónicas que un tutor puede utilizar. Tercero, propone diferentes estrategias pedagógicas que un tutor puede implementar para enseñar a los estudiantes en línea.
El documento ofrece consejos para que los padres contrarresten la influencia de las pandillas, como pasar tiempo semanalmente con los hijos, establecer responsabilidades familiares, conocer a los amigos de los hijos, y aprender sobre las preocupaciones de los jóvenes. También recomienda diferenciar la disciplina de la venganza, no asumir sino preguntar para comprender a los hijos, y permitir cometer errores para aprender juntos.
The document provides an overview of the author's work experience in electronics, quality management, and machine tool service across various employers over several decades. Some of the key roles and responsibilities included:
- Troubleshooting and repairing electrical/electronic systems on NC and CNC machine tools.
- Setting up quality programs to improve quality and reduce waste costs, including statistical inspection, reliability testing, and service reporting systems.
- Managing operations for a machine tool distributor, including field service, sales, marketing, and new product introductions.
- Serving as quality engineer for a defense contractor, overseeing material review and weapon system assembly procedures.
- Providing technical support and participating in product
The document discusses private browsing modes in browsers and mismatches between how they are marketed and how they actually function. It proposes a new web extension, KEEPrivate, to better align user expectations of privacy and anonymity with the actual level of protection provided. KEEPrivate aims to simplify blocking of third-party trackers and cookies with an easy-to-use interface. A survey found users expect private browsing to be anonymous and untraceable, but it does not fully prevent tracking due to limitations of existing private modes.
The document discusses the benefits of exercise for mental health. Regular physical activity can help reduce anxiety and depression and improve mood and cognitive function. Exercise causes chemical changes in the brain that may help protect against mental illness and improve symptoms for those who already suffer from conditions like anxiety and depression.
This document discusses key aspects of entrepreneurship including common myths and facts about entrepreneurs, definitions of entrepreneurship, the types of entrepreneurs, reasons for becoming an entrepreneur, and how to develop entrepreneurial skills. Some key points are that entrepreneurs are not necessarily rich or young, but rather take risks to pursue new opportunities. Entrepreneurship benefits both individuals by creating wealth and countries by generating jobs and economic growth. Developing entrepreneurial skills requires a focus on customers, offerings, money and gaining knowledge from books, websites and discussions.
El documento habla sobre trabajo productivo de tecnología. Enfatiza la importancia de usar la tecnología de manera eficiente y productiva para lograr objetivos. Recomienda herramientas tecnológicas que pueden ayudar a aumentar la productividad como programas de planificación, herramientas de colaboración y aplicaciones móviles.
El documento describe las etapas del desarrollo prenatal desde la concepción hasta el nacimiento, incluyendo cambios en las primeras semanas como la formación del cerebro, corazón y médula espinal, y más adelante el desarrollo de brazos, piernas, ojos y oídos. Explica los cambios en las semanas siguientes como el crecimiento de dedos y pelos, y rotación de intestinos. Al final del embarazo, el feto gana grasa, uñas llegan a las puntas de los dedos,
Este documento describe las etapas del desarrollo de un bebé desde el nacimiento hasta los 10 meses. En los primeros meses, el bebé desarrolla reflejos visuales, táctiles, olfativos y auditivos. A los 3 meses comienza a ser más sociable y a emitir sonidos. A los 6 meses puede agarrar objetos y a los 7 meses babea copiosamente. A los 10 meses se reconoce en el espejo y mejora su motricidad. También describe las etapas del desarrollo psíquico del bebé.
Consejos útiles para que tu hijo sea más feliz (1)Irene Pringle
Este documento ofrece consejos para ayudar a los hijos a estudiar de manera efectiva. Explica que existen cuatro factores que afectan el éxito académico: factores internos como la capacidad y motivación del estudiante; factores ambientales como el lugar de estudio; hábitos de estudio como tener un horario fijo; y técnicas de estudio como el método ELSER3 para leer, subrayar y memorizar la información. Los padres pueden influir en estos factores al proporcionar un espacio de estudio adec
Global Startup Creators vol.5 - Facebook bot development handsonTakuya Tejima
This document provides instructions for setting up a Facebook chat bot using Node.js and Express. It includes steps for creating a Facebook page, installing Node.js dependencies, setting up the app directory structure, connecting to GitHub, deploying to Heroku, setting up webhook verification, and receiving and responding to messages with the bot. The coding section explains how to set up the webhook endpoint, receive messages, set the access token, and post messages back to Facebook. Deployment involves pushing the code to Heroku and subscribing the Facebook page to the webhook. Customizing the bot is also mentioned.
How to start a business on a ramen noodle budgetFelecia Hatcher
Felecia Hatcher and Derick Pearson the Chief Popsicles of Feverish Ice Cream shows you how to start small and finish big! How to Start a business on a Ramen Noodle Budget! This is perfect for college students! Now is the time to start a business don't let money be an obstacle when you can get creative with your limited resources and catapult your dreams into a BADASS BUSINESS! Remember a recession is a terrible thing to waste!
Pharmacokinetics / Biopharmaceutics - Multi compartment IV bolusAreej Abu Hanieh
This document discusses multicompartment models used to describe drug distribution and elimination kinetics. A two-compartment model includes a central compartment representing highly perfused tissues and blood, and a peripheral tissue compartment with slower drug distribution. The plasma concentration curve following intravenous administration has an initial rapid distribution phase as the drug distributes between compartments, followed by a slower elimination phase as the drug is removed from the central compartment. Rate constants describe drug transfer between compartments, and parameters like volume of distribution and half-life can be estimated from the curve.
This document summarizes 4 abstracts from the AROICON 2018 conference:
1. The first abstract describes a protocol for using cone beam CT with an extended longitudinal field of view to localize and adaptively verify treatment along the craniospinal axis for radiotherapy. It found the extended CBCT method provided accurate localization and dosimetric verification.
2. The second abstract involves developing a Python script to evaluate treatment plan robustness using both physical and radiobiological parameters for proton pencil beam scanning. The script allowed quick evaluation of perturbed dose distributions.
3. The third abstract reports on clinical implementation of deep inspiration breath hold amplitude gating for stereotactic body radiotherapy of lung and liver oligome
Perfusion and dynamic contrast enhanced mrifahad shafi
This document discusses dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) techniques for measuring tissue perfusion. It describes how DCE-MRI analyzes the passage of gadolinium contrast agents through tissue over time to provide quantitative measurements of microvascular properties like permeability and blood flow. The document outlines the principles, image acquisition, and qualitative, semi-quantitative, and quantitative analysis methods for DCE-MRI. It also discusses applications for evaluating brain tumors and other disorders.
This document discusses several microfluidic separation methods for isolating circulating tumor cells (CTCs) from blood. It describes how microfluidics can accurately manipulate flow conditions to efficiently separate CTCs from blood cells based on differences in their biophysical properties such as size and deformability. Using these microfluidic approaches, viable CTCs can be retrieved from cancer patient blood samples with high isolation efficiency and purity. Identification of CTCs aids in cancer detection, disease monitoring, and insights into metastasis. The document also discusses using magnetic nanoparticles coupled with doxorubicin chemotherapy drug and an external magnetic field to more effectively deliver the drug to breast cancer cells and increase mortality rates.
This study uses a mathematical model to optimize radiation fractionation schedules by allowing fraction sizes to vary over time. The model accounts for how tumor geometry, sensitivity, and repopulation change as the tumor shrinks during treatment. Optimizing fraction sizes increased the tumor control probability from 0.7 to 0.966. The optimal schedule used larger fractions on Friday afternoons to compensate for weekend breaks, with afternoon fractions being larger than morning fractions. Fraction sizes also escalated over the course of treatment as the tumor became more sensitive and grew faster.
El documento ofrece consejos para que los padres contrarresten la influencia de las pandillas, como pasar tiempo semanalmente con los hijos, establecer responsabilidades familiares, conocer a los amigos de los hijos, y aprender sobre las preocupaciones de los jóvenes. También recomienda diferenciar la disciplina de la venganza, no asumir sino preguntar para comprender a los hijos, y permitir cometer errores para aprender juntos.
The document provides an overview of the author's work experience in electronics, quality management, and machine tool service across various employers over several decades. Some of the key roles and responsibilities included:
- Troubleshooting and repairing electrical/electronic systems on NC and CNC machine tools.
- Setting up quality programs to improve quality and reduce waste costs, including statistical inspection, reliability testing, and service reporting systems.
- Managing operations for a machine tool distributor, including field service, sales, marketing, and new product introductions.
- Serving as quality engineer for a defense contractor, overseeing material review and weapon system assembly procedures.
- Providing technical support and participating in product
The document discusses private browsing modes in browsers and mismatches between how they are marketed and how they actually function. It proposes a new web extension, KEEPrivate, to better align user expectations of privacy and anonymity with the actual level of protection provided. KEEPrivate aims to simplify blocking of third-party trackers and cookies with an easy-to-use interface. A survey found users expect private browsing to be anonymous and untraceable, but it does not fully prevent tracking due to limitations of existing private modes.
The document discusses the benefits of exercise for mental health. Regular physical activity can help reduce anxiety and depression and improve mood and cognitive function. Exercise causes chemical changes in the brain that may help protect against mental illness and improve symptoms for those who already suffer from conditions like anxiety and depression.
This document discusses key aspects of entrepreneurship including common myths and facts about entrepreneurs, definitions of entrepreneurship, the types of entrepreneurs, reasons for becoming an entrepreneur, and how to develop entrepreneurial skills. Some key points are that entrepreneurs are not necessarily rich or young, but rather take risks to pursue new opportunities. Entrepreneurship benefits both individuals by creating wealth and countries by generating jobs and economic growth. Developing entrepreneurial skills requires a focus on customers, offerings, money and gaining knowledge from books, websites and discussions.
El documento habla sobre trabajo productivo de tecnología. Enfatiza la importancia de usar la tecnología de manera eficiente y productiva para lograr objetivos. Recomienda herramientas tecnológicas que pueden ayudar a aumentar la productividad como programas de planificación, herramientas de colaboración y aplicaciones móviles.
El documento describe las etapas del desarrollo prenatal desde la concepción hasta el nacimiento, incluyendo cambios en las primeras semanas como la formación del cerebro, corazón y médula espinal, y más adelante el desarrollo de brazos, piernas, ojos y oídos. Explica los cambios en las semanas siguientes como el crecimiento de dedos y pelos, y rotación de intestinos. Al final del embarazo, el feto gana grasa, uñas llegan a las puntas de los dedos,
Este documento describe las etapas del desarrollo de un bebé desde el nacimiento hasta los 10 meses. En los primeros meses, el bebé desarrolla reflejos visuales, táctiles, olfativos y auditivos. A los 3 meses comienza a ser más sociable y a emitir sonidos. A los 6 meses puede agarrar objetos y a los 7 meses babea copiosamente. A los 10 meses se reconoce en el espejo y mejora su motricidad. También describe las etapas del desarrollo psíquico del bebé.
Consejos útiles para que tu hijo sea más feliz (1)Irene Pringle
Este documento ofrece consejos para ayudar a los hijos a estudiar de manera efectiva. Explica que existen cuatro factores que afectan el éxito académico: factores internos como la capacidad y motivación del estudiante; factores ambientales como el lugar de estudio; hábitos de estudio como tener un horario fijo; y técnicas de estudio como el método ELSER3 para leer, subrayar y memorizar la información. Los padres pueden influir en estos factores al proporcionar un espacio de estudio adec
Global Startup Creators vol.5 - Facebook bot development handsonTakuya Tejima
This document provides instructions for setting up a Facebook chat bot using Node.js and Express. It includes steps for creating a Facebook page, installing Node.js dependencies, setting up the app directory structure, connecting to GitHub, deploying to Heroku, setting up webhook verification, and receiving and responding to messages with the bot. The coding section explains how to set up the webhook endpoint, receive messages, set the access token, and post messages back to Facebook. Deployment involves pushing the code to Heroku and subscribing the Facebook page to the webhook. Customizing the bot is also mentioned.
How to start a business on a ramen noodle budgetFelecia Hatcher
Felecia Hatcher and Derick Pearson the Chief Popsicles of Feverish Ice Cream shows you how to start small and finish big! How to Start a business on a Ramen Noodle Budget! This is perfect for college students! Now is the time to start a business don't let money be an obstacle when you can get creative with your limited resources and catapult your dreams into a BADASS BUSINESS! Remember a recession is a terrible thing to waste!
Pharmacokinetics / Biopharmaceutics - Multi compartment IV bolusAreej Abu Hanieh
This document discusses multicompartment models used to describe drug distribution and elimination kinetics. A two-compartment model includes a central compartment representing highly perfused tissues and blood, and a peripheral tissue compartment with slower drug distribution. The plasma concentration curve following intravenous administration has an initial rapid distribution phase as the drug distributes between compartments, followed by a slower elimination phase as the drug is removed from the central compartment. Rate constants describe drug transfer between compartments, and parameters like volume of distribution and half-life can be estimated from the curve.
This document summarizes 4 abstracts from the AROICON 2018 conference:
1. The first abstract describes a protocol for using cone beam CT with an extended longitudinal field of view to localize and adaptively verify treatment along the craniospinal axis for radiotherapy. It found the extended CBCT method provided accurate localization and dosimetric verification.
2. The second abstract involves developing a Python script to evaluate treatment plan robustness using both physical and radiobiological parameters for proton pencil beam scanning. The script allowed quick evaluation of perturbed dose distributions.
3. The third abstract reports on clinical implementation of deep inspiration breath hold amplitude gating for stereotactic body radiotherapy of lung and liver oligome
Perfusion and dynamic contrast enhanced mrifahad shafi
This document discusses dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) techniques for measuring tissue perfusion. It describes how DCE-MRI analyzes the passage of gadolinium contrast agents through tissue over time to provide quantitative measurements of microvascular properties like permeability and blood flow. The document outlines the principles, image acquisition, and qualitative, semi-quantitative, and quantitative analysis methods for DCE-MRI. It also discusses applications for evaluating brain tumors and other disorders.
This document discusses several microfluidic separation methods for isolating circulating tumor cells (CTCs) from blood. It describes how microfluidics can accurately manipulate flow conditions to efficiently separate CTCs from blood cells based on differences in their biophysical properties such as size and deformability. Using these microfluidic approaches, viable CTCs can be retrieved from cancer patient blood samples with high isolation efficiency and purity. Identification of CTCs aids in cancer detection, disease monitoring, and insights into metastasis. The document also discusses using magnetic nanoparticles coupled with doxorubicin chemotherapy drug and an external magnetic field to more effectively deliver the drug to breast cancer cells and increase mortality rates.
This study uses a mathematical model to optimize radiation fractionation schedules by allowing fraction sizes to vary over time. The model accounts for how tumor geometry, sensitivity, and repopulation change as the tumor shrinks during treatment. Optimizing fraction sizes increased the tumor control probability from 0.7 to 0.966. The optimal schedule used larger fractions on Friday afternoons to compensate for weekend breaks, with afternoon fractions being larger than morning fractions. Fraction sizes also escalated over the course of treatment as the tumor became more sensitive and grew faster.
Clinical Applications of Proton MR Spectroscopy.pdfSilvana Ciardullo
1) Proton MR spectroscopy provides greater tissue characterization than MR imaging alone by detecting metabolic abnormalities. It can be performed on most clinical 1.5T MR units in 10-15 minutes without significant additional scan time.
2) The technique detects metabolite concentrations based on peak intensities and locations on generated spectra graphs. The most commonly detected brain metabolites are NAA, creatine, choline, and lactate. Abnormal concentrations of these metabolites can indicate various neurological conditions.
3) Proton MR spectroscopy is useful for evaluating tumors, infections, demyelinating diseases, and other neurological disorders by detecting deviations from normal metabolite levels and ratios that provide physiological information about tissue status.
1. Microdialysis is a technique that allows measurement of unbound drug concentrations in extracellular fluids by using a probe with a semipermeable membrane. The relationship between drug concentrations in the dialysate and surrounding tissue depends on various in vivo factors and cannot be determined by in vitro recovery alone.
2. Many techniques have been developed to quantify in vivo concentrations from microdialysis data, including accounting for recovery, diffusion through tissue, and exchange between tissue compartments.
3. Mathematical models of the microdialysis process treat recovery as dependent on diffusion resistances in the probe lumen, membrane and external tissue environment. These models provide insights into how tissue properties influence recovery.
Variation of dose distribution with depth and incident energy using EGSnrc Mo...iosrjce
IOSR Journal of Applied Physics (IOSR-JAP) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of physics and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications in applied physics. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
1. The document proposes a formalism to utilize clinically available MRI imaging data for early detection of resistance to targeted cancer therapies.
2. By extracting tumor growth parameters from serial MRI scans, mathematical models can be used to predict future tumor growth and identify signs of resistance earlier than current methods.
3. Simulated data is used to determine the number and frequency of scans needed to reliably extract parameters and detect resistance under different levels of initial resistance and sampling intervals.
This document discusses pharmacokinetic models used to describe drug distribution in the body over time. It describes how pharmacokinetic models divide the body into compartments representing organs or tissues and use differential equations to model drug concentration changes based on blood flow and other parameters. The document outlines several types of pharmacokinetic models including blood flow-limited models, models incorporating drug binding, and diffusion-limited models. It provides examples of drugs that typically use blood flow-limited models and notes how accounting for interspecies differences in drug binding can help predict human pharmacokinetics.
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The document discusses issues with computational scientific software and proposes a solution called Digital Scientific Notations. Current scientific software is difficult to test and validate due to a lack of specifications and documentation. This makes the software results unverifiable and prevents comparison of different models. The proposed Digital Scientific Notations would embed computational models and methods into scholarly documents using a formal programming language. This would allow models to be precisely defined, validated, and compared, addressing current verification and reproducibility problems in computational science.
This paper investigates the shell properties and concentration stability of a new acoustofluidic delivery agent liposome in comparison to DefinityTM microbubbles. Frequency dependent attenuation measurements were used to estimate the shell stiffness (Sp) and friction (Sf) parameters of both agents. The liposome had lower Sp and Sf values compared to DefinityTM microbubbles. Temperature increase resulted in decreased Sf for both agents but increased Sp for liposomes and decreased Sp for microbubbles. Size distribution measurements using tunable resistive pulse sensing showed the liposomes maintained >80% concentration for 24 hours at physiological temperature, while microbubbles maintained only 27% over the same period.
This study compared one- and two-compartment kinetic models in dynamic contrast-enhanced MRI of hepatocellular carcinomas (HCC). While both models produced similar results in normal liver tissue, the one-compartment model overestimated transfer constants in highly arterialized HCC lesions by not accounting for vascular components. Both models differentiated between liver and tumor tissue based on parameters like Ktrans1, with the two-compartment model also distinguishing based on vascular plasma volume. Therefore, a two-compartment model is necessary for accurate analysis of HCC lesions due to their arterial dominance.
Life Expectancy Estimate with Bivariate Weibull Distribution using Archimedea...CSCJournals
Archimedean copulas are used to construct bivariate Weibull distributions. Co-movement structures of variables are analyzed through the copulas, where the tail dependence between the variables is explored with more flexibility. Based on the distance between the copula distribution and its empirical version, a copula that may best fit data is selected. With extra computing costs, the adequacy of the copula chosen is then assessed. When multiple myeloma data are considered, it is found that relationship between survival time of a patient and the hemoglobin level is well described by the Clayton copula. The bivariate Weibull distribution constructed by the copula is used to estimate value at risk from which we investigate the anticipated longest life expectancy of a patient with the disease over the treatment period.
Limitations and Advantages in Assessing Adenovirus Homogeneity by Laser Light...KBI Biopharma
The document discusses methods for characterizing the homogeneity of adenovirus preparations using analytical techniques like light scattering and analytical ultracentrifugation. It finds that light scattering has limitations in accurately assessing particle size distribution and aggregation when measuring large virus particles like adenovirus. Analytical ultracentrifugation is able to provide higher resolution information about the adenovirus particle size distribution and detect different forms of structural heterogeneity.
Ben Kelty Summer Research Poster Presentation Benjamin Kelty
The document summarizes research using multiple spectroscopic techniques to study the unfolding of the protein horse heart cytochrome c. A 33-step titration protocol was used to unfold the protein with guanidine hydrochloride while monitoring it with circular dichroism, fluorescence, and absorbance spectroscopy. Data from the wild type protein and two mutants was analyzed to determine Gibbs free energy and the concentration of denaturant when half the protein is unfolded. Comparing unfolding curves of wild type and mutants provides insight into how different regions of the protein unfold. Future work will apply this protocol to 11 additional cytochrome c mutants.
This document discusses estimating blood volume flow in precapillary microvessels in the rabbit mesentery based on axial erythrocyte velocity measurements. It summarizes:
1) Volume flow was estimated in 30 microvessels with diameters between 5.6-12 μm by measuring instantaneous axial blood velocity throughout the cardiac cycle and averaging. The effect of velocity profile variation with diameter was also taken into account.
2) According to Murray's law, volume flow should be proportional to diameter to the fourth power. Curve fitting to the volume flow and diameter data supported this relationship, validating the hypothesis that the principle of constant longitudinal pressure gradient applies in the precapillary microvasculature.
3) A
This document summarizes research on mathematical modeling of brain tumor growth and invasion. It discusses early models of tumor growth and diffusion that assumed homogeneous brain tissue. Later models incorporated brain heterogeneity by allowing different diffusion rates in grey and white matter. An example application uses a partial differential equation model and high performance computing to predict brain tumor growth. Cellular automata models are also described that simulate cancer growth and proliferation as a complex, chaotic dynamical system. Biomagnetic measurements provide evidence of low-dimensional chaotic dynamics in cancer lesions.
1. Simulation and Modeling of the Impacts of Nanoparticle Size on Nanoparticle
Mediated Drug Delivery to Brain Tumor
Daniel Kurniawan
Department of Chemical and Biomolecular Engineering, National University of Singapore, 4
Engineering Drive 4, Singapore 117576, Singapore
ABSTRACT
Nanoparticle can be used as a polymeric carrier to effectively deliver a chemotherapeutic drug
for brain tumor treatments by bypassing the blood brain barrier. In this study, we employ a com-
putational fluid dynamics simulation to study the influence of nanoparticle size to the temporal
and spatial nanoparticle concentration profile in brain. The study used the convection-diffusion
model to describe the nanoparticle transport. Idealized geometry brain and tumor model is used as
the domain of the simulation. Literature review is conducted to establish the correlation between
nanoparticle size with both nanoparticle diffusion coefficient and drug release rate in order to show
its effect on the concentration profile. The temporal variation analysis shows that smaller nanopar-
ticle can reach a steady-state concentration condition at a faster rate with a lower volume-averaged
concentration. The spatial variation analysis shows that smaller nanoparticle size encompasses a
larger, albeit insignificant, volume of distribution at steady state with a smaller maximum nanopar-
ticle concentration in both brain and tumor region.
INTRODUCTION
In 2016, nearly 78,000 new cases of brain tumors are expected to be diagnosed in which nearly
25,000 of them are malignant (American Brain Tumor Association , 2015). The most common
strategy to treat brain tumors usually involves surgical removal, chemotherapy, and radiotherapy.
For chemotherapy, though the drug is biologically effective to treat brain tumor, drug transport
properties are often overlooked. Effective delivery of therapeutic agents to tumor cells is essen-
tial to the success of chemotherapy, especially the brain tumor treatment because of the various
obstacles.
One challenging problem that drug delivery by systemic administration is facing is the blood
brain barrier (BBB). The current practice to bypasses the BBB is to use a polymeric system infused
directly into the tumor site, achieving a localized drug delivery. This study particularly focuses on
the usage of nanoparticles as a drug-loaded polymeric carrier which will be infused directly into
the tumor site by a needle to enhance the treatment outcome. With the advance of nanotechnology,
polymeric nanoparticles can be employed as carriers to transport the entrapped or adsorbed drugs
across the BBB. Also, nanoparticles systems may also be useful in protecting the drug from a
biological degradation prior to its release. As a result, more sustained release of therapeutic drug
to treat brain tumor can be achieved. The primary goal of this study is to analyze the temporal
1
2. and spatial nanoparticle concentration profile infused in brain by the means of computational fluid
dynamic (CFD) simulations.
The emphasis of this study is to conduct a parametric study to examine the impact of nanopar-
ticle size to nanoparticle concentration distribution in brain. Two important transport properties
which are directly influenced by nanoparticle sizes are the nanoparticle diffusivity coefficient and
the drug release rate. Therefore, it is necessary to study the impact of nanoparticle on both proper-
ties first. With an established correlation between nanoparticle sizes and both nanoparticle diffu-
sivity and drug release rate, we will then examine how changing both parameters simultaneously,
based on the correlation, will impact the temporal and spatial nanoparticle concentration profile.
MATHEMATICAL MODEL
Equation
The brain interstitial fluid flow is described by coupling the modified continuity and momentum
equation for fluid flow in a porous medium. The continuity equation for incompressible interstitial
fluid in the brain tissue is:
· v = FV (1)
where v is superficial interstitial fluid velocity vector and FV is the rate of fluid gain from the
capillary bed per unit volume of tissue. Fluid removal by the lymphatic system is not included
because brain tissue lacks a well-defined lymphatic system. The fluid gain is assumed to be a
non-uniformly distributed source, depending on the pressure difference between blood vessels
and interstitial fluid. The constitutive equation for FV follows Starling’s law (Baxter , 1989):
FV = Lp(S/V )[pv − pi − σ(πv − πi)] (2)
where Lp is hydraulic conductivity of the microvascular wall, pV is vascular pressure, pi is inter-
stitial fluid pressure, S/V is available exchange area of the blood vessels per unit volume of tissue,
σ is the osmotic reflection coefficient for plasma proteins, and πv and πi are osmotic pressures of
blood plasma and interstitial fluid, respectively.
The brain tissue is assumed to be a rigid porous medium. The momentum equation for fluid
flow through tissue is assumed to be:
ρ
∂v
∂t
+ v · v = − pi + µ 2
v −
µ
K
v (3)
where t is time, ρ and µ are density and viscosity of the interstitial fluid and K is the Darcy
permeability of the tissue.
Nanoparticle availability is governed by a generic convection-diffusion equation with a source
/ elimination term. Thus, the nanoparticle conservation equation, to be coupled with the interstitial
fluid flow equations, is as follows:
∂C
∂t
= Di
2
C − · (vC) + S (4)
where C is the nanoparticle concentration , Di is nanoparticle diffusivity in interstitial space and
S is the source / elimination term.
2
3. (a) (b) (c)
Figure 1. The idealized model geometry used in the simulation, showing the presence of ventricle
(shown in blue), tumor (green), and the remaining brain tissue (red). (a) The complete 3-D sim-
ulation domain of brain. (b) Zoomed-in isometric view of tumor region and needle. (c) The mid
cross sectional of simulation domain, containing all brain, tumor, and ventricle region, used for
representative 2-D visualization throughout this study.
The nanoparticle source / elimination term is contributed by drug release rate and nanoparticle
degradation rate. It is assumed that nanoparticles will be eliminated when drug is released from
nanoparticle or the nanoparticle itself is degraded. For simplicity, both drug release rate and
nanoparticle degradation rate follows the first-order kinetic model. Therefore, nanoparticle source
/ elimination term can be described by equation as follows:
S = −(krel + ke)C (5)
where krel and ke are the first-order elimination constant for nanoparticle concentration due to
drug release rate and degradation respectively.
Geometry
This study uses an idealized three-dimensional model to describe the brain geometry domain
used in the simulation. Fig. 1a and 1b depicts the 3-D geometry while Fig. 1c depicts its 2-D
representations. There are three main regions in the simulation domain: brain, tumor and ven-
tricle. Each region is modeled as a sphere with radius 66 mm, 10 mm and 18.5 mm respectively.
Spherical geometry is used as an idealized geometry model while keeping the volume region to
be as realistic as possible. In other words, the volume of the brain region in this simulation is
approximately equal to the average real brain volume of human.
The simulation also assume an idealized needle insertion position. Needle is inserted in the
center of tumor region (Fig. 1b). Needle wall penetrates both the brain and tumor region. The
inlet diameter of the needle is 1 mm long.
Model Parameter
The discussion about baseline values of parameters related to the interstitial fluid flow (Eq. (1),
(2), and (3)) is available on several previous studies on drug transport simulation (Arifin , 2009),
(Arifin , 2009). To study the effects of nanoparticle sizes on nanoparticle transport (Eq. (4) and
3
4. Eq. (5)), we will vary nanoparticle diffusivity (Di) and drug release rate (krel) since these two
parameters are directly affected by nanoparticle sizes. In this particular case study, the value of
the drug degradation constant (ke) is assumed to be 5 × 10−6
s−1
.
Nanoparticle Diffusivity Stokes-Einstein equation can model nanoparticle diffusivity in intersti-
tial fluid accurately. The study conducted by Cu (2009) shows that the Stokes-Einstein equation
can predict the diffusion coefficient of PLGA nanoparticles with diameter 170 ± 57 nm loaded
with green-fluorescent Coumarin-6 molecules in water. The special form of Stokes-Einstein equa-
tion for a spherical particles is as follows:
DAB =
kT
6πµBrA
(6)
where DAB is the diffusion coefficient of nanoparticle (A) in interstitial fluid (B), k is the Boltz-
mann’s constant, T is the absolute temperature, µB is the dynamic viscosity of interstitial fluid and
rA is the radius of the spherical nanoparticle. In our case study, it is assumed that T is the body
temperature (310.15 K) and the viscosity of interstitial fluid is 0.000 78 kg m−1
s−1
(Perry , 1996).
We will use this inverse relationship to establish the correlation between diffusion coefficient and
the radius of any type of nanoparticle.
Drug Release Rate Drug release rate coefficient (krel) in Eq. (5) can be determined by looking at
the commonly documented drug release profile of a nanoparticle. The drug release rate, following
the first-order kinetic law, can be described as follows:
r =
∂C
∂t
= −
1
DL
∂Cd
∂t
= −krelC (7)
where r is the release rate, Cd is the concentration of drug, and DL is the drug loading, which is
a measure of the amount of drug loaded per mass of nanoparticles.
Hence, we can get the corresponding model of the drug release profile by solving Eq. (7)
for Cd. With this assumption of the first order kinetic law, drug release profile should be an
exponential equation as follows:
Cd = A(1 − e−krelt
) (8)
where A is a lumped solution constant and krel is the coefficient that we are interested in. We
will fit the drug release profile available from literature to obtain krel coefficient dependency to
nanoparticle sizes. Note that krel will not only be influenced by nanoparticle size exclusively,
it also depends on many other important factor such as nanoparticle formulation and drug type.
Therefore, available data from literature must be chosen carefully to isolate the relationship be-
tween nanoparticle sizes and drug release rate.
Pandey (2016) conducted a study to evaluate the performance of Tamoxifen embedded PLGA
nanoparticles (PLGA-Tmx) as an anticancer drug vehicle. In the study, similar PLGA-Tmx
nanoparticles are prepared with varying dimension of 17 nm to 30 nm by changing the con-
centration of polymer, emulsifier, and drug. In this case, PLGA concentration of 10 mg mL−1
,
20 mg mL−1
and 30 mg mL−1
used for the nanoparticle fabrication resulted in particles with diam-
eter of 19.8 nm, 21.4 nm and 24.2 nm respectively. Drug release profile of different nanoparticle
size is recorded (Fig. 2a).
4
5. (a) (b)
Figure 2. Invitro sustained release of drug fabricated using different PLGA concentration, which
resulted in different PLGA-Tmx size; PLGA concentration of 10 mg mL−1
, 20 mg mL−1
and
30 mg mL−1
used for the nanoparticle fabrication resulted in particles with diameter of 19.8 nm,
21.4 nm and 24.2 nm respectively. (a) The original figure of drug release profile in the literature.
(b) Best exponential model fit of the drug release profile data.
The cumulative drug release profile were best fitted with the exponential equation in Eq. (8)
leading to a time constant value (krel) of 1.72 × 10−5
s−1
(r2
= 0.86) for PLGA-Tmx nanoparticle
with a diameter of 19.8 nm prepared from 10 mg mL−1
of PLGA. On the other hand, a lower best-
fit values of time constant (krel) are observed from nanoparticle with bigger sizes: 1.14 × 10−5
s−1
and 8.43 × 10−6
s−1
(r2
= 0.94; 0.96) for PLGA-Tmx nanoparticle with a diameter of 21.4 nm
and 24.2 nm prepared from 20 mg mL−1
and 30 mg mL−1
of PLGA respectively. The higher
values of time constant (krel) implies that drug can be released from the nanoparticle carriers at a
faster rate. It is qualitatively consistent with the fact that smaller nanoparticle will have a larger
surface area per unit volume to release the loaded drugs; hence, it is capable of releasing drugs at
a faster rate. Fig. 2b shows the comparison between experimental data and the fitted data. This
dependency result between krel and nanoparticle sizes will be used as a model parameter in the
simulation. Linear interpolation is used to obtain krel of nanoparticles with different sizes.
Boundary Conditions
Interstitial fluid flow is solved using a pressure based boundary condition in the ventricle sur-
face and brain periphery. The ventricle surface will be the high pressure domain while brain
periphery will be the low pressure domain. In particular, interstitial fluid is constantly infused at
a constant pressure (pventricle = 1447.4 Pa ). At the same time, the outermost boundary condition
is the pressure at the arachnoid villi (pouter = 667 Pa) where the fluid is removed (Kimelberg ,
2004). Along the internal boundaries between brain and tumor region, conditions of continuity
are imposed. At the needle wall in both brain and tumor region, no-slip conditions are applied.
At the inlet of the needle, nanoparticle is injected with a constant fluid flow velocity condition at
0.000 106 m s−1
.
The boundary conditions for nanoparticle concentration involves no-flux conditions on both
ventricle surface and brain periphery. Along the internal boundaries between brain and tumor
region, conditions of continuity are imposed. No-flux conditions are also applied at the needle
5
6. Table 1. Simulation Group
Group Size (nm) Di (m2
s−1
) krel (s−1
) ke (s−1
)
1 19.8 2.94 × 10−11
1.72 × 10−5
5 × 10−6
2 20.6 2.83 × 10−11
1.37 × 10−5
5 × 10−6
3 21.4 2.72 × 10−11
1.14 × 10−5
5 × 10−6
4 22.8 2.55 × 10−11
9.70 × 10−6
5 × 10−6
5 24.2 2.41 × 10−11
8.42 × 10−6
5 × 10−6
Figure 3. Temporal variation of volume-averaged nanoparticle concentration in tumor region
wall in both brain and tumor region. At the inlet of the needle, nanoparticle is injected at a
constant nanoparticle concentration at 4 kg m−3
SIMULATION METHOD
Based on the correlation study on nanoparticle transport parameters, we run 5 different groups
of simulation to observe the effect of nanoparticle size on nanoparticle concentration temporal
and spatial profile. Table 1 completely summarized the simulation parameters for nanoparticle
transport for each group.
Simulation were conducted using ANSYS Fluent 16.2. The simulation is carried out using Eq.
(1), (2), and (3) to solve for interstitial fluid transport and Eq. (4) and (5) to solve for nanoparticle
transport. In this study, the simulation is carried out in a complete 3-D domain. However, for
this specific ideal geometry cases (symmetric sphere), 2-D axisymmetric model, with the top-half
circle of Fig. 1c as the simulation domain, can actually be used to reduce the computational effort.
6
7. Table 2. Simulation Group Exponential Fit [Model: y = A(1 − e−kt
)]
Group Size (nm) A (kg m−3
) k (s−1
) R2
1 19.8 0.870 8.81 × 10−5
0.97
2 20.6 0.896 8.68 × 10−5
0.97
3 21.4 0.914 8.61 × 10−5
0.97
4 22.8 0.928 8.54 × 10−5
0.97
5 24.2 0.938 8.51 × 10−5
0.97
RESULTS AND DISCUSSION
Temporal Variation of Volume-averaged Nanoparticle Concentration Profile
To examine the transient profile, we will look at the temporal variation of volume-averaged
nanoparticle concentration in tumor region. Volume-averaged nanoparticle concentration in tu-
mor region for all 5 simulation groups is plotted in Fig. 3. Exponential model (similar to Eq.
(8)) is employed to gain a better understanding of the transient concentration profile. The result
of exponential best-fit for each group is summarized in Table 2 with A as the lumped solution
constant and k as the time constant value.
As nanoparticle size become larger, it can be clearly observed that the steady state averaged
concentration profile increases; the value of A, which corresponds to the concentration value at
time infinity, increases as the nanoparticle size increases. It can be explained by the fact that
smaller nanoparticle sizes corresponds to a higher release rate coefficient. It implies that smaller
nanoparticle does not need as high concentration as the larger one to achieve a similar elimination
rate required in the steady state.
In the exponential model, time constant k indicates how long does it take for the volume-
averaged concentration to reach steady state. The higher values of time constant (k) implies that
steady state condition of nanoparticle concentration can be achieved at a faster rate. The best
exponential fit shows that smaller nanoparticle has a higher time constant; i.e. it is faster for
a smaller nanoparticle to reach its steady state condition. This constant might be an important
parameter to control if one wants to design a drug that can be released in a sustained manner.
Spatial Variation of Steady-state Nanoparticle Concentration Profile
To examine the spatial profile, we will look at the spatial variation of steady-state nanoparticle
concentration. Comparison of steady state nanoparticle concentration profile between simulation
group 1, 3 and 5 is shown in Fig. 4. At a glance, there does not seem to be any difference 3 group
of contour. With a more meticulous observation, one can see a subtle difference between them.
However, it is safe to say that the steady state concentration profile is not sensitive to changes in
nanoparticle size.
As nanoparticle size become larger, the steady state concentration profile encompasses a larger
area (or volume in 3-D). It agrees with the previous quantitative observation that steady state
volume averaged concentration increases as nanoparticle size become larger. Convection plays a
larger role as nanoparticle size decreases because the diffusivity of nanoparticle decreases. The
more significant role of convective flows can explain the larger concentration profile surrounding
the inlet.
7
8. (a) (b) (c)
Figure 4. Steady state nanoparticle concentration profile of: (a) group 1 (d = 19.8 nm) (b) group
3 (d = 21.4 nm) (c) group 5 (d = 24.2 nm).
Maximum Concentration of Nanoparticle
The simulation result shows that the maximum nanoparticle concentration in tumor region is
6.022 kg m−3
, 6.036 kg m−3
and 6.054 kg m−3
for group 1, 3 and 5 respectively. On the other hand,
the maximum nanoparticle concentration in the brain region (non-tumor region) is 0.681 kg m−3
,
0.761 kg m−3
and 0.811 kg m−3
for group 1, 3 and 5 respectively.
As nanoparticle size become larger, the maximum nanoparticle concentration, both in brain
and tumor region, increases. While one might want to reach a specific concentration threshold to
achieve a therapeutic effect, a lower concentration of nanoparticle in the brain region (non-tumor
region) might be desirable if we want to minimize the toxicity of the treatment. It should be noted
that the dependency of maximum nanoparticle concentration to nanoparticle size in brain region
is much higher than those in tumor region; maximum nanoparticle concentration in brain region
decreases at a much faster rate for a smaller nanoparticle. This might be another parameter that
need to be considered and controlled when designing the drug.
CONCLUSION
This computational modeling effort enables the prediction and understanding of nanoparticle
drug distribution in human brain. However, models are not without assumptions and simplifica-
tion. In reality, the brain tissue in not homogeneous in nature; therefore, the transport means, such
as diffusion and convective flow, will be more likely to be anisotropic and spatially varied (Lin-
niger , 2008). Idealized geometry is also used in this current model, a more realistic geometry of
human brain is desired for a more accurate simulation. We also make a number of assumptions in
the mathematical model used to simplify the simulation, such as the first-order law for the release
kinetic. A research on a more accurate model can lead to a more realistic simulation result. Fi-
nally, a more thorough independent parameter study of drug release rate and diffusivity coefficient
might need to be conducted in order to gain a better understanding of the effect of each individual
transport properties.
This simulation study has provided an insight toward how nanoparticle size effect its temporal
and spatial distribution when infused in brain. Nanoparticle size can be an important design
parameter to control if we want to fabricate a new drug delivery method to treat brain tumor using
nanoparticle carriers. On the other hand, nanoparticle concentration profile can give an insight
8
9. on how drug is distributed throughout the brain and tumor. The predicated drug concentrations
can be used to evaluate the treatment effectiveness. With this understanding, a more efficient drug
transport can be achieved.
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