scholarly journals High complexity cellular barcoding and clonal tracing reveals stochastic and deterministic parameters of radiation resistance

Author(s):  
Anne Wursthorn ◽  
Christian Schwager ◽  
Ina Kurth ◽  
Claudia Peitzsch ◽  
Christel Herold‐Mende ◽  
...  
2020 ◽  
Author(s):  
Anne Wursthorn ◽  
Christian Schwager ◽  
Ina Kurth ◽  
Claudia Peitzsch ◽  
Christel Herold-Mende ◽  
...  

AbstractThe impact of functional heterogeneity in response to radiation therapy is poorly understood to the present. It remains elusive whether clonal selection of tumor cells in response to ionizing radiation (IR) is a deterministic or stochastic process. We applied high-resolution lentiviral cellular barcoding for quantitative clonal tracking and deconvolution of clonal dynamics in response to IR. Clonal tracking of over 400.000 HNSCC patient-derived tumor cells and the analyses of over 1500 million sequencing reads in clonogenic survival assays reveals that fractionated IR induced a strong selective pressure for clonal reduction. This significantly exceeded uniform clonal survival probabilities indicative for a strong clone-to clone difference within tumor cell lines. IR induced clonal reduction affected the majority of tumor cells ranging between 96-75% and correlated to the degree of radiation sensitivity. Survival and clonogenicity is characterized by an intensive clonal distortion and dominance of individual tumor cells. Survival to IR is driven by a deterministic clonal selection of a smaller population which commonly survives radiation, while increased clonogenic capacity is a result of clonal competition of cells which have been selected stochastically. A 2-fold increase in radiation resistance results in a 4-fold (p<0.05) higher deterministic clonal selection showing that the ratio of these parameters is amenable to radiation sensitivity which correlates to prognostic biomarkers of HNSCC. Evidence for the existence of a rare subpopulation with an intrinsically radiation resistant phenotype commonly surviving IR was found at a frequency of 0.6-3.3% (p<0.001, FDR 3%). With cellular barcoding we introduce a novel functional heterogeneity associated qualitative readout for tracking dynamics of clonogenic survival in response to radiation. This enables the quantification of intrinsically radiation resistant tumor cells from patient samples and reveals the contribution of stochastic and deterministic clonal selection processes in response to IR.


2015 ◽  
Vol 227 (03) ◽  
Author(s):  
AK Elder ◽  
O Heidenreich ◽  
HJ Vormoor
Keyword(s):  

2019 ◽  
pp. 40-47
Author(s):  
E. A. Mironchik

The article discusses the method of solving the task 18 on the Unified State Examination in Informatics (Russian EGE). The main idea of the method is to write the conditions of the problem utilizing the language of formal logic, using elementary predicates. According to the laws of logic the resulting complex logical expression would be transformed into an expression, according to which a geometric model is supposed to be constructed which allows to obtain an answer. The described algorithm does allow high complexity problem to be converted into a simple one.


2015 ◽  
Vol 0 (1) ◽  
Author(s):  
Yuliya A. Kazimirenko ◽  
Valentina V. Shlapatskaya
Keyword(s):  

2012 ◽  
Vol 22 (3) ◽  
pp. 219-232 ◽  
Author(s):  
Luca Belmonte ◽  
Eugenia Pechkova ◽  
Shailesh Tripathi ◽  
Dora Scudieri ◽  
Claudio Nicolini

Author(s):  
R.K. Babichev ◽  
◽  
G.V. Babicheva ◽  
K.V. Levendorskij ◽  
◽  
...  

Author(s):  
Felix Beaudoin ◽  
Stephen Lucarini ◽  
Fred Towler ◽  
Stephen Wu ◽  
Zhigang Song ◽  
...  

Abstract For SRAMs with high logic complexity, hard defects, design debug, and soft defects have to be tackled all at once early on in the technology development while innovative integration schemes in front-end of the line are being validated. This paper presents a case study of a high-complexity static random access memory (SRAM) used during a 32nm technology development phase. The case study addresses several novel and unrelated fail mechanisms on a product-like SRAM. Corrective actions were put in place for several process levels in the back-end of the line, the middle of the line, and the front-end of the line. These process changes were successfully verified by demonstrating a significant reduction of the Vmax and Vmin nest array block fallout, thus allowing the broader development team to continue improving random defectivity.


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