scholarly journals A spatial cell culture model for predicting chemotherapy dosing strategies

2019 ◽  
Author(s):  
Shu Zhu ◽  
Dhruba Deb ◽  
Tal Danino
Keyword(s):  
Spatial Dynamics ◽  
Optimal Dose ◽  
Cell Types ◽  
Three Dimensions ◽  
Model Systems ◽  
Breast Cancer Cell Lines ◽  
Cell Populations ◽  
Dimensional System ◽  
Two Dimensional ◽  
Dosing Strategies

AbstractPredicting patient responses to chemotherapy regimens is a major challenge in cancer treatment. To do this requires quantitative mathematical models to predict optimal dose and frequency for a particular drug, and experimental model systems such as three-dimensional organoids that accurately recapitulate the tumor microenvironment and heterogeneity. However, tracking the spatial dynamics of multiple cell types in three-dimensions can be a significant challenge in terms of time and throughput. Here we develop a two-dimensional system that allows for simple tracking of cell populations via fluorescence microscopy for modeling spatial dynamics in tumors. We first develop multiple 4T1 breast cancer cell lines resistant to varying concentrations of doxorubicin, and demonstrate how well mixed and spatially heterogeneous populations expand in a two-dimensional colony. We subject cell populations to varied dose and frequency of chemotherapy and measure colony growth radius and populations. We then build a mathematical model to describe the dynamics of both chemosensitive and chemoresistant populations, where we determine which number of doses can produce the smallest tumor size based on parameters in the system. In the future, this system can be adapted to quickly optimize dosing strategies in the setting of heterogeneous cell types or patient derived cells with varied chemoresistance.

scholarly journals Artificial kagome spin ice: dimensional reduction, avalanche control and emergent magnetic monopoles

2012 ◽  
Vol 370 (1981) ◽  
pp. 5767-5782 ◽  
Author(s):  
R. V. Hügli ◽  
G. Duff ◽  
B. O'Conchuir ◽  
E. Mengotti ◽  
A. Fraile Rodríguez ◽  
...  
Keyword(s):  
Data Storage ◽  
Dimensional Reduction ◽  
Magnetic Monopoles ◽  
Real Space ◽  
Model Systems ◽  
Dimensional System ◽  
Two Dimensional ◽  
Spin Ice ◽  
Artificial Spin Ice ◽  
String Formation

Artificial spin-ice systems consisting of nanolithographic arrays of isolated nanomagnets are model systems for the study of frustration-induced phenomena. We have recently demonstrated that monopoles and Dirac strings can be directly observed via synchrotron-based photoemission electron microscopy, where the magnetic state of individual nanoislands can be imaged in real space. These experimental results of Dirac string formation are in excellent agreement with Monte Carlo simulations of the hysteresis of an array of dipoles situated on a kagome lattice with randomized switching fields. This formation of one-dimensional avalanches in a two-dimensional system is in sharp contrast to disordered thin films, where avalanches associated with magnetization reversal are two-dimensional. The self-organized restriction of avalanches to one dimension provides an example of dimensional reduction due to frustration. We give simple explanations for the origin of this dimensional reduction and discuss the disorder dependence of these avalanches. We conclude with the explicit demonstration of how these avalanches can be controlled via locally modified anisotropies. Such a controlled start and stop of avalanches will have potential applications in data storage and information processing.

Role of inflammation in the development of colorectal cancer

2020 ◽  
Vol 20 ◽  
Author(s):  
Sridhar Muthusami ◽  
R. Ileng Kumaran ◽  
Kokelavani Nampalli Babu ◽  
Sneha Krishnamoorthy ◽  
Akash Guruswamy ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Chronic Inflammation ◽  
Interleukin 1 ◽  
Cell Types ◽  
Model Systems ◽  
Cytokine Gene Expression ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Proinflammatory Molecules

: Chronic inflammation can lead to the development of many diseases including cancer. Inflammatory bowel disease (IBD) that includes both ulcerative colitis (UC) and Crohn's disease (CD) are risk factors for the development of colorectal cancer (CRC). Many cytokines produced primarily by the gut immune cells either during or in response to localized inflammation in the colon and rectum are known to stimulate the complex interactions between the different cell types in the gut environment resulting in acute inflammation. Subsequently, chronic inflammation together with genetic and epigenetic changes has been shown to lead to the development and progression of CRC. Various cell types present in the colon such as enterocytes, Paneth cells, goblet cells and macrophages express receptors for inflammatory cytokines and respond to tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6 and other cytokines. Among the several cytokines produced, TNF-α and IL-1β are the key proinflammatory molecules that play critical roles in the development of CRC. The current review is intended to consolidate the published findings to focus on the role of proinflammatory cytokines, namely TNF-α and IL-1β, on inflammation (and the altered immune response) in the gut, to better understand the development of CRC in IBD, using various experimental model systems, preclinical and clinical studies. Moreover, this review also highlights the current therapeutic strategies available (monotherapy and combination therapy), to alleviate the symptoms or treat inflammationassociated CRC by using monoclonal antibodies or aptamers to block proinflammatory molecules, inhibitors of tyrosine kinases in inflammatory signaling cascade, competitive inhibitors of proinflammatory molecules, and the nucleic acid drugs like small activating RNAs (saRNAs) or microRNA (miRNA) mimics to activate tumor suppressor or repress oncogene/proinflammatory cytokine gene expression.

scholarly journals BMS field theories and Weyl anomaly

2021 ◽  
Vol 2021 (7) ◽  
Author(s):  
Arjun Bagchi ◽  
Sudipta Dutta ◽  
Kedar S. Kolekar ◽  
Punit Sharma
Keyword(s):  
Three Dimensions ◽  
Field Theories ◽  
Partition Functions ◽  
Two Dimensional ◽  
Speed Of Light ◽  
Asymptotically Flat ◽  
Weyl Invariance ◽  
Flat Spacetimes ◽  
Liouville Action ◽  
Null Surfaces

Abstract Two dimensional field theories with Bondi-Metzner-Sachs symmetry have been proposed as duals to asymptotically flat spacetimes in three dimensions. These field theories are naturally defined on null surfaces and hence are conformal cousins of Carrollian theories, where the speed of light goes to zero. In this paper, we initiate an investigation of anomalies in these field theories. Specifically, we focus on the BMS equivalent of Weyl invariance and its breakdown in these field theories and derive an expression for Weyl anomaly. Considering the transformation of partition functions under this symmetry, we derive a Carrollian Liouville action different from ones obtained in the literature earlier.

scholarly journals Topological correlators and surface defects from equivariant cohomology

2020 ◽  
Vol 2020 (9) ◽  
Author(s):  
Rodolfo Panerai ◽  
Antonio Pittelli ◽  
Konstantina Polydorou
Keyword(s):  
Quantum Mechanics ◽  
Equivariant Cohomology ◽  
Surface Defects ◽  
Star Product ◽  
Three Dimensional ◽  
Three Dimensions ◽  
Dimensional System ◽  
The Novel ◽  
One Dimensional ◽  
Dual Quantum

Abstract We find a one-dimensional protected subsector of $$ \mathcal{N} $$ N = 4 matter theories on a general class of three-dimensional manifolds. By means of equivariant localization we identify a dual quantum mechanics computing BPS correlators of the original model in three dimensions. Specifically, applying the Atiyah-Bott-Berline-Vergne formula to the original action demonstrates that this localizes on a one-dimensional action with support on the fixed-point submanifold of suitable isometries. We first show that our approach reproduces previous results obtained on S3. Then, we apply it to the novel case of S2× S1 and show that the theory localizes on two noninteracting quantum mechanics with disjoint support. We prove that the BPS operators of such models are naturally associated with a noncom- mutative star product, while their correlation functions are essentially topological. Finally, we couple the three-dimensional theory to general $$ \mathcal{N} $$ N = (2, 2) surface defects and extend the localization computation to capture the full partition function and BPS correlators of the mixed-dimensional system.

scholarly journals Single-cell transcriptomic analysis of mIHC images via antigen mapping

2021 ◽  
Vol 7 (10) ◽  
pp. eabc5464
Author(s):  
Kiya W. Govek ◽  
Emma C. Troisi ◽  
Zhen Miao ◽  
Rachael G. Aubin ◽  
Steven Woodhouse ◽  
...  
Keyword(s):  
Single Cell ◽  
Spatial Patterns ◽  
Cell Types ◽  
Level Of Detail ◽  
Cell Populations ◽  
Sequencing Data ◽  
Spatially Resolved ◽  
Murine Spleen ◽  
Single Cell Rna Sequencing ◽  
Antibody Panel

Highly multiplexed immunohistochemistry (mIHC) enables the staining and quantification of dozens of antigens in a tissue section with single-cell resolution. However, annotating cell populations that differ little in the profiled antigens or for which the antibody panel does not include specific markers is challenging. To overcome this obstacle, we have developed an approach for enriching mIHC images with single-cell RNA sequencing data, building upon recent experimental procedures for augmenting single-cell transcriptomes with concurrent antigen measurements. Spatially-resolved Transcriptomics via Epitope Anchoring (STvEA) performs transcriptome-guided annotation of highly multiplexed cytometry datasets. It increases the level of detail in histological analyses by enabling the systematic annotation of nuanced cell populations, spatial patterns of transcription, and interactions between cell types. We demonstrate the utility of STvEA by uncovering the architecture of poorly characterized cell types in the murine spleen using published cytometry and mIHC data of this organ.

scholarly journals Large organized chromatin lysine domains help distinguish primitive from differentiated cell populations

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Seyed Ali Madani Tonekaboni ◽  
Benjamin Haibe-Kains ◽  
Mathieu Lupien
Keyword(s):  
Transposable Elements ◽  
Histone Modifications ◽  
Cell Types ◽  
Regulatory Elements ◽  
Cell Populations ◽  
Genomic Features ◽  
Differentiated Cells ◽  
Chromatin Interactions ◽  
Topologically Associating Domains ◽  
Highly Expressed Genes

AbstractThe human genome is partitioned into a collection of genomic features, inclusive of genes, transposable elements, lamina interacting regions, early replicating control elements and cis-regulatory elements, such as promoters, enhancers, and anchors of chromatin interactions. Uneven distribution of these features within chromosomes gives rise to clusters, such as topologically associating domains (TADs), lamina-associated domains, clusters of cis-regulatory elements or large organized chromatin lysine (K) domains (LOCKs). Here we show that LOCKs from diverse histone modifications discriminate primitive from differentiated cell types. Active LOCKs (H3K4me1, H3K4me3 and H3K27ac) cover a higher fraction of the genome in primitive compared to differentiated cell types while repressive LOCKs (H3K9me3, H3K27me3 and H3K36me3) do not. Active LOCKs in differentiated cells lie proximal to highly expressed genes while active LOCKs in primitive cells tend to be bivalent. Genes proximal to bivalent LOCKs are minimally expressed in primitive cells. Furthermore, bivalent LOCKs populate TAD boundaries and are preferentially bound by regulators of chromatin interactions, including CTCF, RAD21 and ZNF143. Together, our results argue that LOCKs discriminate primitive from differentiated cell populations.

scholarly journals Energetics of mesoscale cell turbulence in two-dimensional monolayers

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Shao-Zhen Lin ◽  
Wu-Yang Zhang ◽  
Dapeng Bi ◽  
Bo Li ◽  
Xi-Qiao Feng
Keyword(s):  
Kinetic Energy ◽  
Tumor Metastasis ◽  
Cell Types ◽  
Boltzmann Distribution ◽  
Scaling Exponent ◽  
Biological Processes ◽  
Two Dimensional ◽  
Cell Monolayers ◽  
Wide Range ◽  
Epithelial Cell Monolayers

AbstractInvestigation of energy mechanisms at the collective cell scale is a challenge for understanding various biological processes, such as embryonic development and tumor metastasis. Here we investigate the energetics of self-sustained mesoscale turbulence in confluent two-dimensional (2D) cell monolayers. We find that the kinetic energy and enstrophy of collective cell flows in both epithelial and non-epithelial cell monolayers collapse to a family of probability density functions, which follow the q-Gaussian distribution rather than the Maxwell–Boltzmann distribution. The enstrophy scales linearly with the kinetic energy as the monolayer matures. The energy spectra exhibit a power-decaying law at large wavenumbers, with a scaling exponent markedly different from that in the classical 2D Kolmogorov–Kraichnan turbulence. These energetic features are demonstrated to be common for all cell types on various substrates with a wide range of stiffness. This study provides unique clues to understand active natures of cell population and tissues.

Sign in / Sign up

Export Citation Format

Share Document