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An early phase clinical trial is the first step in evaluating the effects in humans of a potential new anti-disease agent or combination of agents. Usually called "phase I" or "phase I/II" trials, these experiments typically have the…

Methodology · Statistics 2010-12-01 Peter F. Thall

We analyze the macroscopic behavior of multi-populations randomly connected neural networks with interaction delays. Similar to cases occurring in spin glasses, we show that the sequences of empirical measures satisfy a large deviation…

Mathematical Physics · Physics 2015-06-15 Tanguy Cabana , Jonathan Touboul

There is a widening recognition that cancer cells are products of complex developmental processes. Carcinogenesis and metastasis formation are increasingly described as systems-level, network phenomena. Here we propose that malignant…

Molecular Networks · Quantitative Biology 2013-09-18 David M. Gyurko , Daniel V. Veres , Dezso Modos , Katalin Lenti , Tamas Korcsmaros , Peter Csermely

The evolutionary and ecological dynamics of tumors under immune responses and therapeutic interventions pose major challenges to long-term treatment success. Although treatment may initially achieve short-term disease control, resistant…

Quantitative Methods · Quantitative Biology 2026-04-03 Nazanin Mokari , Bryce Morsky

In order to analyze data from cancer genome sequencing projects, we need to be able to distinguish causative, or "driver," mutations from "passenger" mutations that have no selective effect. Toward this end, we prove results concerning the…

Populations and Evolution · Quantitative Biology 2013-02-13 Rick Durrett

Consider an epidemic model with a constant flux of susceptibles, in a situation where the corresponding deterministic epidemic model has a unique stable endemic equilibrium. For the associated stochastic model, whose law of large numbers…

Probability · Mathematics 2020-03-06 Etienne Pardoux

We analyse numerically the effects of small population size in the initial transient regime of a simple example population dynamics. These effects play an important role for the numerical determination of large deviation functions of…

Statistical Mechanics · Physics 2017-09-28 Esteban Guevara Hidalgo , Vivien Lecomte

Cancer is a complex disease and thus is complicated to model. However, simple models that describe the main processes involved in tumoral dynamics, e.g., competition and mutation, can give us clues about cancer behaviour, at least…

Dynamical Systems · Mathematics 2014-11-25 V. Castillo , J. Tomas Lazaro , J. Sardanyes

Stem cells have the potential to produce lineages of non-stem cell populations (differentiated cells) via a ubiquitous hierarchal division scheme. Differentiation of a stem cell into (partially) differentiated cells can happen either…

Cell Behavior · Quantitative Biology 2014-11-07 Kamran Kaveh , Mohammad Kohandel , Siv Sivaloganathan

We investigate exceedances of the process over a sufficiently high threshold. The exceedances determine the risk of hazardous events like climate catastrophes, huge insurance claims, the loss and delay in telecommunication networks. Due to…

Statistics Theory · Mathematics 2015-01-08 Natalia Markovich

Drug resistance and metastasis - the major complications in cancer - both entail adaptation of cancer cells to stress, whether a drug or a lethal new environment. Intriguingly, these adaptive processes share similar features that cannot be…

Molecular Networks · Quantitative Biology 2021-09-28 Aseel Shomar , Omri Barak , Naama Brenner

We propose a method for determining the most likely cause, in terms of conventional generator outages and renewable fluctuations, of power system frequency reaching a predetermined level that is deemed unacceptable to the system operator.…

Systems and Control · Electrical Eng. & Systems 2020-05-26 Brendan Patch , Bert Zwart

We present and establish large deviations principles for general multivariate renewal-reward processes associated with a classical discrete-time renewal process. A renewal-reward process describes a cumulative reward over time, supposing…

Mathematical Physics · Physics 2019-04-11 Marco Zamparo

Practically, all chemotherapeutic agents lead to drug resistance. Clinically, it is a challenge to determine whether resistance arises prior to, or as a result of, cancer therapy. Further, a number of different intracellular and…

Populations and Evolution · Quantitative Biology 2014-12-03 Jana L. Gevertz , Zahra Aminzare , Kerri-Ann Norton , Judith Perez-Velazquez , Alexandria Volkening , Katarzyna A. Rejniak

Phenotypic heterogeneity in cancer cells is widely observed and is often linked to drug resistance. In several cases, such heterogeneity in drug sensitivity of tumors is driven by stochastic and reversible acquisition of a drug tolerant…

Molecular Networks · Quantitative Biology 2019-01-28 Niraj Kumar , Gwendolyn M. Cramer , Seyed Alireza Zamani Dahaj , Bala Sundaram , Jonathan P. Celli , Rahul V. Kulkarni

The unwelcome evolution of malignancy during cancer progression emerges through a selection process in a complex heterogeneous population structure. In the present work, we investigate evolutionary dynamics in a phenotypically heterogeneous…

Populations and Evolution · Quantitative Biology 2018-02-07 Ali Mahdipour Shirayeh , Kamran Kaveh , Mohammad Kohandel , Siv Sivaloganathan

We investigate exceedances of the process over a sufficiently high threshold. The exceedances determine the risk of hazardous events like climate catastrophes, huge insurance claims, the loss and delay in telecommunication networks. Due to…

Statistics Theory · Mathematics 2017-10-03 Natalia Markovich

The emergence of a predominant phenotype within a cell population is often triggered by a rare accumulation of DNA mutations in a single cell. For example, tumors may be initiated by a single cell in which multiple mutations cooperate to…

Tissues and Organs · Quantitative Biology 2018-11-21 Philip Greulich , Benjamin D. Simons

We investigate large deviations for the empirical measure of the forward and backward recurrence time processes associated with a classical renewal process with arbitrary waiting-time distribution. The Donsker-Varadhan theory cannot be…

Probability · Mathematics 2010-09-22 Raphael Lefevere , Mauro Mariani , Lorenzo Zambotti

Cancer progression is an example of a rapid adaptive process where evolving new traits is essential for survival and requires a high mutation rate. Precancerous cells acquire a few key mutations that drive rapid population growth and…

Populations and Evolution · Quantitative Biology 2015-06-18 Christopher McFarland , Leonid Mirny , Kirill S. Korolev