Predicting Cell Death and Mutation Frequency for a Wide Spectrum of LET by Assuming DNA Break Clustering Inside Repair Domains

Cosmic radiation, which is composed of high charged and energy (HZE) particles, is responsible for cell death and mutation, which may be involved in cancer induction. Mutations are consequences of mis-repaired DNA breaks especially double-strand breaks (DSBs) that induce inter- and intra-chromosomal rearrangements (translocations, deletions, inversion). In this study, a computer simulation model is used to investigate the clustering of DSBs in repair domains, previously evidenced by our group in human breast cells [1]. This model is calibrated with experimental data measuring persistent 53BP1 radiation-induced foci (RIF) and is used to explain the high relative biological effectiveness (RBE) of HZE for both cell death and DNA mutation frequencies. We first validate our DSB cluster model using a new track structure model deployed on a simple geometrical configuration for repair domains in the nucleus; then we extend the scope from cell death to mutation induction. This work suggests that mechanism based on DSB repair process can explain several biological effects induced by HZE particles on different type of living cell

Dynamic Exploration of Networks: from general principles to the traceroute process

Dynamical processes taking place on real networks define on them evolving subnetworks whose topology is not necessarily the same of the underlying one. We investigate the problem of determining the emerging degree distribution, focusing on a class of tree-like processes, such as those used to explore the Internet's topology. A general theory based on mean-field arguments is proposed, both for single-source and multiple-source cases, and applied to the specific example of the traceroute exploration of networks. Our results provide a qualitative improvement in the understanding of dynamical sampling and of the interplay between dynamics and topology in large networks like the Internet.Comment: 13 pages, 6 figure

DNA Repair Domain Modeling Can Predict Cell Death and Mutation Frequency for Wide Range Spectrum of Radiation

Exploration missions to Mars and other destinations raise many questions about the health of astronauts. The continuous exposure of astronauts to galactic cosmic rays is one of the main concerns for long-term missions. Cosmic ionizing radiations are composed of different ions of various charges and energies notably, highly charged energy (HZE) particles. The HZE particles have been shown to be more carcinogenic than low-LET radiation, suggesting the severity of chromosomal aberrations induced by HZE particles is one possible explanation. However, most mathematical models predicting cell death and mutation frequency are based on directly fitting various HZE dose response and are in essence empirical approaches. In this work, we assume a simple biological mechanism to model DNA repair and use it to simultaneously explain the low- and high-LET response using the exact same fitting parameters. Our work shows that the geometrical position of DNA repair along tracks of heavy ions are sufficient to explain why high-LET particles can induce more death and mutations. Our model is based on assuming DNA double strand breaks (DSBs) are repaired within repair domain, and that any DSBs located within the same repair domain cluster into one repair unit, facilitating chromosomal rearrangements and increasing the probability of cell death. We introduced this model in 2014 using simplified microdosimetry profiles to predict cell death. In this work, we collaborated with NASA Johnson Space Center to generate more accurate microdosimetry profiles derived by Monte Carlo techniques, taking into account track structure of HZE particles and simulating DSBs in realistic cell geometry. We simulated 224 data points (D, A, Z, E) with the BDSTRACKS model, leading to a large coverage of LET from ~10 to 2,400 keV/m. This model was used to generate theoretical RBE for various particles and energies for both cell death and mutation frequencies. The RBE LET dependence is in agreement with experimental data known in human and murine cells. It suggests that cell shape and its orientation with respect to the HZE particle beam can modify the biological response to radiation. Such discovery will be tested experimentally and, if proven accurate, will be another strong supporting evidence for DNA repair domains and their critical role in interpreting cosmic radiation sensitivity

Mining Partially-Ordered Sequential Rules Common to Multiple Sequences

© 2015 IEEE. Sequential rule mining is an important data mining problem with multiple applications. An important limitation of algorithms for mining sequential rules common to multiple sequences is that rules are very specific and therefore many similar rules may represent the same situation. This can cause three major problems: (1) similar rules can be rated quite differently, (2) rules may not be found because they are individually considered uninteresting, and (3) rules that are too specific are less likely to be used for making predictions. To address these issues, we explore the idea of mining "partially-ordered sequential rules" (POSR), a more general form of sequential rules such that items in the antecedent and the consequent of each rule are unordered. To mine POSR, we propose the RuleGrowth algorithm, which is efficient and easily extendable. In particular, we present an extension (TRuleGrowth) that accepts a sliding-window constraint to find rules occurring within a maximum amount of time. A performance study with four real-life datasets show that RuleGrowth and TRuleGrowth have excellent performance and scalability compared to baseline algorithms and that the number of rules discovered can be several orders of magnitude smaller when the sliding-window constraint is applied. Furthermore, we also report results from a real application showing that POSR can provide a much higher prediction accuracy than regular sequential rules for sequence prediction

Discovering High-Utility Itemsets at Multiple Abstraction Levels

High-Utility Itemset Mining (HUIM) is a relevant data mining task. The goal is to discover recurrent combinations of items characterized by high prot from transactional datasets. HUIM has a wide range of applications among which market basket analysis and service proling. Based on the observation that items can be clustered into domain-specic categories, a parallel research issue is generalized itemset mining. It entails generating correlations among data items at multiple abstraction levels. The extraction of multiple-level patterns affords new insights into the analyzed data from dierent viewpoints. This paper aims at discovering a novel pattern that combines the expressiveness of generalized and High-Utility itemsets. According to a user-defined taxonomy items are rst aggregated into semantically related categories. Then, a new type of pattern,namely the Generalized High-utility Itemset (GHUI), is extracted. It represents a combinations of items at different granularity levels characterized by high prot (utility). While protable combinations of item categories provide interesting high-level information, GHUIs at lower abstraction levels represent more specic correlationsamong protable items. A single-phase algorithm is proposed to efficiently discover utility itemsets at multiple abstraction levels. The experiments, which were performed on both real and synthetic data, demonstrate the effectiveness and usefulness of the proposed approach

Learning Behavioral Representations of Human Mobility

In this paper, we investigate the suitability of state-of-the-art representation learning methods to the analysis of behavioral similarity of moving individuals, based on CDR trajectories. The core of the contribution is a novel methodological framework, mob2vec, centered on the combined use of a recent symbolic trajectory segmentation method for the removal of noise, a novel trajectory generalization method incorporating behavioral information, and an unsupervised technique for the learning of vector representations from sequential data. Mob2vec is the result of an empirical study conducted on real CDR data through an extensive experimentation. As a result, it is shown that mob2vec generates vector representations of CDR trajectories in low dimensional spaces which preserve the similarity of the mobility behavior of individuals.Comment: ACM SIGSPATIAL 2020: 28th ACM SIGSPATIAL International Conference on Advances in Geographic Information Systems.November 2020 Seattle, Washington, US

Bethe-Peierls approximation and the inverse Ising model

We apply the Bethe-Peierls approximation to the problem of the inverse Ising model and show how the linear response relation leads to a simple method to reconstruct couplings and fields of the Ising model. This reconstruction is exact on tree graphs, yet its computational expense is comparable to other mean-field methods. We compare the performance of this method to the independent-pair, naive mean- field, Thouless-Anderson-Palmer approximations, the Sessak-Monasson expansion, and susceptibility propagation in the Cayley tree, SK-model and random graph with fixed connectivity. At low temperatures, Bethe reconstruction outperforms all these methods, while at high temperatures it is comparable to the best method available so far (Sessak-Monasson). The relationship between Bethe reconstruction and other mean- field methods is discussed

USGS National Hydrologic Model: Continental Scale Modeling for Decision-making, Research, and Education

A comprehensive understanding of physical processes that affect streamflow is required to effectively manage water resources to meet present and future human and environmental needs. Water resources management from local to national scales can benefit from a consistent, process-based watershed modeling capability. The National Hydrologic Model (NHM), which was developed by the U.S. Geological Survey to support coordinated, comprehensive, and consistent hydrologic modeling at multiple scales for the conterminous United States, provides this essential capability. The NHM fills knowledge gaps in ungaged areas to disseminate nationally-consistent, locally informed, stakeholder relevant results. The NHM provides scientists, water resource managers, and the public knowledge to advance basic scientific inquiry, enable more informed and effective decision-making, and provide an educational resource to learn about all components of the water balance. In the future, as understanding of hydrologic processes allows for improved algorithms and data sets, the NHM will continue to evolve to better support the nation’s water-resources research, decision making, and education needs