scholarly journals Quantifying the Dynamics of Hematopoiesis by In Vivo IdU Pulse‐Chase, Mass Cytometry, and Mathematical Modeling

2019 ◽  
Vol 95 (10) ◽  
pp. 1075-1084
Author(s):  
Amir Erez ◽  
Ratnadeep Mukherjee ◽  
Grégoire Altan‐Bonnet
Keyword(s):  
Mathematical Modeling ◽  
Mass Cytometry

scholarly journals Quantifying the dynamics of hematopoiesis by in vivo IdU pulse-chase, mass cytometry and mathematical modeling

2019 ◽  
Author(s):  
Amir Erez ◽  
Ratnadeep Mukherjee ◽  
Alexandre Day ◽  
Pankaj Mehta ◽  
Grégoire Altan-Bonnet
Keyword(s):  
Mathematical Modeling ◽  
Direct Detection ◽  
Binary Classification ◽  
Mouse Strains ◽  
Mass Cytometry ◽  
Experimental Conditions ◽  
Minimal Impact ◽  
Wide Range

AbstractWe present a new method to directly quantify the dynamics of differentiation of multiple cellular subsets in unperturbed mice. We combine a pulse-chase protocol of IdU injections with subsequent analysis by mass cytometry (CyTOF), and mathematical modeling of the IdU dynamics. Measurements by CyTOF allow for a wide range of cells to be analyzed at once, due to the availability of a large staining panel without the complication of fluorescence spill-over. These are also compatible with direct detection of integrated iodine signal, with minimal impact on immunophenotyping based on surface markers. Mathematical modeling beyond a binary classification of surface marker abundance allows for a continuum of cellular states as the cells transition from one state to another. Thus, we present a complete and robust method for directly quantifying differentiation at the systemic level, allowing for system-wide comparisons between different mouse strains and/or experimental conditions.

OPTIMIZATION AND ASSESSMENT OF THE IN VIVO EFFICACY OF A HEPARIN-REMOVING BIOREACTOR USING MATHEMATICAL MODELING

ASAIO Journal ◽  
1996 ◽  
Vol 42 (2) ◽  
pp. 58
Author(s):  
Youngro Byun ◽  
Tanya Wang ◽  
Jae-Seung Kim ◽  
Victor C. Yang
Keyword(s):  
Mathematical Modeling ◽  
In Vivo Efficacy

Current trends in mathematical modeling of tumor–microenvironment interactions: a survey of tools and applications

2010 ◽  
Vol 235 (4) ◽  
pp. 411-423 ◽  
Author(s):  
Katarzyna A Rejniak ◽  
Lisa J McCawley
Keyword(s):  
Mathematical Modeling ◽  
Protein Interactions ◽  
Computational Models ◽  
Chemical Species ◽  
Tumor Stroma ◽  
Cellular Functions ◽  
Complex Interactions ◽  
Expanding Population

In its simplest description, a tumor is comprised of an expanding population of transformed cells supported by a surrounding microenvironment termed the tumor stroma. The tumor microcroenvironment has a very complex composition, including multiple types of stromal cells, a dense network of various extracellular matrix (ECM) fibers interpenetrated by the interstitial fluid and gradients of several chemical species that either are dissolved in the fluid or are bound to the ECM structure. In order to study experimentally such complex interactions between multiple players, cancer is dissected and considered at different scales of complexity, such as protein interactions, biochemical pathways, cellular functions or whole organism studies. However, the integration of information acquired from these studies into a common description is as difficult as the disease itself. Computational models of cancer can provide cancer researchers with invaluable tools that are capable of integrating the complexity into organizing principles as well as suggesting testable hypotheses. We will focus in this Minireview on mathematical models in which the whole cell is a main modeling unit. We will present a current stage of such cell-focused mathematical modeling incorporating different stromal components and their interactions with growing tumors, and discuss what modeling approaches can be undertaken to complement the in vivo and in vitro experimentation.

scholarly journals STEM-17. NOT ALL GBM STEM CELLS ARE EQUAL: IMPLICATIONS FOR RESEARCH AND THERAPY

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii199-ii200
Author(s):  
Luciano Galdieri ◽  
Arijita Jash ◽  
Olga Malkova ◽  
Diane Mao ◽  
Jian Campian ◽  
...  
Keyword(s):  
Stem Cells ◽  
Phenotypic Diversity ◽  
Treatment Resistance ◽  
Surface Markers ◽  
Mass Cytometry ◽  
Pathway Activation ◽  
Almost All ◽  
And Function ◽  
Activation Status

Abstract Glioblastoma (GBM) kills almost all patients within 2 years. A subpopulation of cells, GBM stem cells (GSCs), contributes to treatment resistance and recurrence. A major therapeutic goal is to kill GSCs, but no targeted therapy yet exists. Since their discovery, GSCs have been isolated using single surface markers, such as CD15, CD44, CD133, and a-6 integrin. It remains unknown how these single surface marker-defined GSC populations compare to each other in terms of signal transduction and function and whether expression of different combinations of these markers is associated with distinct phenotypes. Using mass cytometry and fresh operating room specimens, we found that 15 distinct GSC subpopulations exist in vivo and they differ in their MEK/ERK, WNT, and AKT pathway activation status. In culture, some subpopulations were lost and previously undetectable ones materialized. GSCs highly expressing all four surface markers had the greatest self-renewal capacity and in vivo tumorigenicity as well as the strongest WNT pathway activation. This work highlights the signaling and phenotypic diversity in GSC subpopulations, together suggesting that not all GSCs are equivalent. These observations should be considered when studying GSCs in the laboratory, with implications for the development of treatments that target GSCs and prevent tumor recurrence in patients.

scholarly journals Dynamics of intraocular temperature during local hypothermia (experimental study and mathematical modeling)

2019 ◽  
pp. 383-388
Author(s):  
Lukyan Anatychuk ◽  
Roman Kobyliansky ◽  
Nataliya Pasyechnikova ◽  
Volodymyr Naumenko ◽  
Oleg Zadorozhnyy ◽  
...  
Keyword(s):  
Mathematical Modeling ◽  
Mathematical Model ◽  
Biological Tissues ◽  
Comsol Multiphysics ◽  
Rabbit Eye ◽  
Local Contact ◽  
Group 2 ◽  
Local Hypothermia ◽  
Group 1

Therapeutic hypothermia currently is successfully in various fields of medicine to protect biological tissues from ischemia. However the issue of changes in intraocular temperature under hypothermia remains poorly understood. Purpose. To study the dynamics of intraocular temperature in conditions of local hypothermia and on the basis of the obtained data to develop a mathematical model of thermophysical processes in the rabbit eye. Materials and methods. An in vivo experiment was performed on 10 rabbits (20 eyes). In group 1 (5 rabbits, 10 eyes), epibulbar and intraocular temperature was measured after local contact hypothermia through closed eyelids, in group 2 (5 rabbits, 10 eyes) after local contact hypothermia directly through the cornea. ока безпосередньо через рогівку. Для гіпотермії застосовувався гелевий акумулятор холоду температурою -10 °С. Для вимірювання температури в різних відділах ока застосовувався термоелектричний пристрій, розроблений Інститутом термоелектрики НАН і МОН України та ДУ «Інститут очних хвороб і тканинної терапії ім. В. П.Філатова НАМН України». Для розробки математичної моделі теплофізичних процесів в оці кролика використано пакет прикладних програм COMSOL Multiphysics. Результати. Температура склоподібного тіла в 1-й і 2-й групі тварин знизилася в порівнянні з вихідними даними відповідно на 2,8 °С і 5,4 °С. Температурний градієнт між зовнішньою поверхнею рогівки і середньою частиною склоподібного тіла ока кролика в 1-й групі становив 7,1 °С, у 2-й групі – 9,2 °С. На підставі отриманих експериментальних даних було розроблено схематичну, математичну та комп’ютерну моделі ока кролика з урахуванням його теплофізичних особливостей, кровообігу, процесів метаболізму і теплообміну. Висновки. У разі локальної контактної гіпотермії очей кролика відбувається зниження епібульбарної температури і температури внутрішньоочних середовищ, як під час охолодження безпосередньо зовнішньої поверхні рогівки, так і під час впливу холоду через закриті повіки. Ключові слова: внутрішньоочна температура, локальна гіпотермія, око кролика, математична модель ока. Для цитування: Анатичук ЛІ, Пасєчнікова НВ, Науменко ВО, Задорожний ОС, Назаретян РЕ, Кобилянський РР, Верешко ЄЮ. Динаміка внутрішньоочної температури в умовах локальної гіпотермії (експериментальне дослідження та математичне моделювання). Журнал Національної академії медичних наук України. 2019;25(4):383–8

scholarly journals 3SDA-01 Measurement-based mathematical modeling of PAR/aPKC-dependent cell polarization in animal development(3SDA Biophysics toward In Vivo work,Symposium)

2013 ◽  
Vol 53 (supplement1-2) ◽  
pp. S104
Author(s):  
Yukinobu Arata ◽  
Michio Hiroshima ◽  
Chan-gi Pack ◽  
Tetsuya J. Kobayashi ◽  
Tatsuo Shibata ◽  
...  
Keyword(s):  
Mathematical Modeling ◽  
Cell Polarization ◽  
Animal Development ◽  
Dependent Cell

scholarly journals In Vivo Bioluminescence Tomography for Monitoring Breast Tumor Growth and Metastatic Spreading: Comparative Study and Mathematical Modeling

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Séverine Mollard ◽  
Raphaelle Fanciullino ◽  
Sarah Giacometti ◽  
Cindy Serdjebi ◽  
Sebastien Benzekry ◽  
...  
Keyword(s):  
Mathematical Modeling ◽  
Tumor Growth ◽  
Comparative Study ◽  
Breast Tumor ◽  
Bioluminescence Tomography ◽  
Metastatic Spreading

scholarly journals Can endothelial hemoglobin-α regulate nitric oxide vasodilatory signaling?

2017 ◽  
Vol 312 (4) ◽  
pp. H854-H866 ◽  
Author(s):  
Jaimit Parikh ◽  
Adam Kapela ◽  
Nikolaos M. Tsoukias
Keyword(s):  
Mathematical Modeling ◽  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Cellular Models ◽  
No Signaling ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

We used mathematical modeling to investigate nitric oxide (NO)-dependent vasodilatory signaling in the arteriolar wall. Detailed continuum cellular models of calcium (Ca2+) dynamics and membrane electrophysiology in smooth muscle and endothelial cells (EC) were coupled with models of NO signaling and biotransport in an arteriole. We used this theoretical approach to examine the role of endothelial hemoglobin-α (Hbα) as a modulator of NO-mediated myoendothelial feedback, as previously suggested in Straub et al. ( Nature 491: 473–477, 2012). The model considers enriched expression of inositol 1,4,5-triphosphate receptors (IP3Rs), endothelial nitric oxide synthase (eNOS) enzyme, Ca2+-activated potassium (KCa) channels and Hbα in myoendothelial projections (MPs) between the two cell layers. The model suggests that NO-mediated myoendothelial feedback is plausible if a significant percentage of eNOS is localized within or near the myoendothelial projection. Model results show that the ability of Hbα to regulate the myoendothelial feedback is conditional to its colocalization with eNOS near MPs at concentrations in the high nanomolar range (>0.2 μM or 24,000 molecules). Simulations also show that the effect of Hbα observed in in vitro experimental studies may overestimate its contribution in vivo, in the presence of blood perfusion. Thus, additional experimentation is required to quantify the presence and spatial distribution of Hbα in the EC, as well as to test that the strong effect of Hbα on NO signaling seen in vitro, translates also into a physiologically relevant response in vivo. NEW & NOTEWORTHY Mathematical modeling shows that although regulation of nitric oxide signaling by hemoglobin-α (Hbα) is plausible, it is conditional to its presence in significant concentrations colocalized with endothelial nitric oxide synthase in myoendothelial projections. Additional experimentation is required to test that the strong effect of Hbα seen in vitro translates into a physiologically relevant response in vivo

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