While resilience of infrastructure networks with fixed size and topology have been quantified using network science methods, the underlying mechanisms have not been elucidated for resilience of dynamic networks that change in size and topology. Using aircraft-to-aircraft (A2A) communication networks, we demonstrate whether and how changes in network size and topology over time affect the resilience of dynamic infrastructure networks. We simulate failure and recovery of spatially constrained A2A communication networks for an airspace region in the U.S. over multiple hourly time windows in a day. These networks were constructed by mapping aircraft locations to nodes and communication channels between aircrafts to edges based on spatial proximity and bandwidth availability. The results imply that the number and relative sizes of the connected network components are key factors affecting the variation in resilience of dynamic networks over time across diverse failure events. Our network science-based simulation approach captures failure patterns of A2A networks beyond an existing analytical model for transportation systems that is limited to locally tree-like random networks. Furthermore, network centrality-based mixed recovery strategies (i.e., betweenness and degree with switching over time) outperform random recovery across multiple hourly time windows. Thus, hourly variability in resilience patterns of A2A communication networks should be a key consideration for developing dynamic airspace transportation risk mitigation insights.

Signalized traffic control problem has been addressed recently with deep Reinforcement Learning (RL) approaches involving diverse state, action, and reward structures. While significant progress has been noted in the literature, open challenges still remain in the areas of adaptive signal phase timing, coordination in a heterogeneous multi-intersection corridor setting, and consideration of real-world traffic conditions. In the context of deep RL-based problem framing, extensions are needed that enable adaptive signal phase timings in an intersection agent's action space, computationally efficient information sharing among neighboring signalized intersection agents along a corridor, and experimentation in realistic simulation environments. In this paper, we develop a deep Advantage Actor Critic (A2C) multi-agent RL (MARL) approach capturing the research extensions above and apply it within a real-world calibrated Aimsun Next traffic corridor simulation model based on traffic data from the City of Coral Gables, Florida. For a heterogeneous multi-intersection corridor control setting, our numerical simulation experiments with a decentralized A2C MARL algorithm applied at different time periods led to a total average corridor travel delay reduction (expressed in seconds/mile averaged over vehicles) from 4.9% to 19.9% compared to state-of-the-art actuated control.

Conformal prediction is a widely used method to quantify the uncertainty of a classifier under the assumption of exchangeability (e.g., IID data). We generalize conformal prediction to the Hidden Markov Model (HMM) framework where the assumption of exchangeability is not valid. The key idea of the proposed method is to partition the non-exchangeable Markovian data from the HMM into exchangeable blocks by exploiting the de Finetti’s Theorem for Markov Chains discovered by Diaconis and Freedman (1980). The permutations of the exchangeable blocks are viewed as randomizations of the observed Markovian data from the HMM. The proposed method provably retains all desirable theoretical guarantees offered by the classical conformal prediction framework in both exchangeable and Markovian settings. In particular, while the lack of exchangeability introduced by Markovian samples constitutes a violation of a crucial assumption for classical conformal prediction, the proposed method views it as an advantage that can be exploited to improve the performance further. Detailed numerical and empirical results that complement the theoretical conclusions are provided to illustrate the practical feasibility of the proposed method.

High-fidelity modeling is an essential design tool for many engineering applications. However, for complex systems, computational cost can be a limiting factor. Analyzing parameter sensitivity, uncertainty quantification, and design optimization require many model evaluations. Surrogate models are often used to develop the relationship between model parameters and quantities of interest. However, in the case of complex systems, surrogate models require several degrees of freedom and, thus, a large number of data points to determine the correct dependencies. For many applications, this may be prohibitively expensive. The reduction of computational requirements can be achieved by leveraging low-fidelity models. Low-fidelity models represent the system at a coarser resolution with the advantage of computational efficiency. Therefore, a bi-fidelity modeling paradigm, which augments the accuracy of a low-fidelity model in a computationally efficient manner by invoking limited runs of a high-fidelity model, can be leveraged to sufficiently balance the accuracy and computational requirements. In this work, a bi-fidelity weighted transfer learning method using neural networks was applied to a computational fluid dynamics heat transfer modeling problem. The transfer learning advantage was investigated as a function of hyperparameters. Our main finding is that the use of a bi-fidelity modeling paradigm achieves accuracy close to that of a high-fidelity Gaussian process model while significantly reducing computational cost. The bi-fidelity model achieves comparable performance with 90 high-fidelity samples-that is, 60% less than the samples needed to achieve similar accuracy without the use of bi-fidelity modeling,

MOTIVATION: The regulation of proteins governs the biological processes and functions and, therefore, the organisms' phenotype. So there is an unmet need for a systematic tool for identifying the proteins that play a crucial role in information processing in a protein-protein interaction (PPI) network. However, the current protein databases and web servers still lag behind to provide an end-to-end pipeline that can leverage the topological understanding of a context-specific PPI network to identify the influential spreaders. Addressing this, we developed a web application, 'konnect2prot' (k2p), which can generate context-specific directional PPI network from the input proteins and detect their biological and topological importance in the network. RESULTS: We pooled together a large amount of ontological knowledge, parsed it down into a functional network, and gained insight into the molecular underpinnings of the disease development by creating a one-stop junction for PPI data. k2p contains both local and global information about a protein, such as protein class, disease mutations, ligands and PDB structure, enriched processes and pathways, multi-disease interactome and hubs and bottlenecks in the directional network. It also identifies spreaders in the network and maps them to disease hallmarks to determine whether they can affect the disease state or not. AVAILABILITY AND IMPLEMENTATION: konnect2prot is freely accessible using the link https://konnect2prot.thsti.in. The code repository is https://github.com/samrat-lab/k2p_bioinfo-2022.

Understanding and early awareness of software vulnerabilities is vital for preventing and mitigating potential impacts from cybersecurity events. One step toward early characterization of software vulnerabilities may involve analyzing discussion and spread of information in online social networks. Prior work has used information from such discussions over multiple online forums to develop dynamic networks among users followed by analysis of structure, spread, and information evolution. In this work, we advance the state-of-the-art by focusing on data-driven learning of types, roles, and transition of roles exhibited by users over time. In social networks, users take on particular roles based on their actions and structure of the network. Identifying “meaningful” roles can help separate potential users of interest from the larger community, and identify patterns in a network relevant for generating early insights into the extent of software vulnerabilities. We identify and compare roles found in online forums (e.g., Twitter) using feature-based Non-negative Matrix Factorization coupled with topological and influence-based measures of centrality. Since users’ activities change over time, we also analyze role evolution in dynamic networks.

Autophagy plays a crucial role in maintaining cellular homeostasis through the degradation of unwanted materials like damaged mitochondria and misfolded proteins. However, the contribution of autophagy toward a healthy cell environment is not only limited to the cleaning process. It also assists in protein synthesis when the system lacks the amino acids' inflow from the extracellular environment due to diet consumptions. Reduction in the autophagy process is associated with diseases like cancer, diabetes, non-alcoholic steatohepatitis, etc., while uncontrolled autophagy may facilitate cell death. We need a better understanding of the autophagy processes and their regulatory mechanisms at various levels (molecules, cells, tissues). This demands a thorough understanding of the system with the help of mathematical and computational tools. The present review illuminates how systems biology approaches are being used for the study of the autophagy process. A comprehensive insight is provided on the application of computational methods involving mathematical modeling and network analysis in the autophagy process. Various mathematical models based on the system of differential equations for studying autophagy are covered here. We have also highlighted the significance of network analysis and machine learning in capturing the core regulatory machinery governing the autophagy process. We explored the available autophagic databases and related resources along with their attributes that are useful in investigating autophagy through computational methods. We conclude the article addressing the potential future perspective in this area, which might provide a more in-depth insight into the dynamics of autophagy.

MOTIVATION: Bistability is one of the salient dynamical features in various all-or-none kinds of decision-making processes. The presence of bistability in a cell signalling network plays a key role in input-output (I/O) relation. Our study is aiming to capture and emphasize the role of motif structure influencing the I/O relation between two nodes in the context of bistability. Here, a model-based analysis is made to investigate the critical conditions responsible for the emergence of different bistable protein-protein interaction (PPI) motifs and their possible applications to find the potential drug-targets. RESULTS: The global sensitivity analysis is used to identify sensitive parameters and their role in maintaining the bistability. Additionally, the bistable switching through hysteresis is explored to develop an understanding of the underlying mechanisms involved in the cell signalling processes, when significant motifs exhibiting bistability have emerged. Further, we elaborate the application of the results by the implication of the emerged PPI motifs to identify potential drug-targets in three cancer networks, which is validated with existing databases. The influence of stochastic perturbations that could hinder desired functionality of any signalling networks is also described here. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Increasing connectivity to the Internet for remote monitoring and control has made cyber-physical systems more vulnerable to deliberate attacks; purely cyber attacks can thereby have physical consequences. Long-term, stealthy attacks such as Stuxnet can be described as Advanced Persistent Threats (APTs). Here, we extend our previous work on hypergames and APTs to develop hypergame-based defender strategies that are robust to deception and do not rely on attack detection. These strategies provide provable bounds—and provably optimal bounds—on the attacker payoff. Strategies based on Bayesian priors do not provide such bounds. We then numerically demonstrate our approach on a building control subsystem and discuss next steps in extending this approach toward an operational capability.

The identification of the Stuxnet worm in 2010 provided a highly publicized example of a cyber attack that physically damaged an industrial control system. This raised public awareness about the possibility of similar attacks against other industrial targets—including critical infrastructure. In this article, we use hypergames to analyze how strategic perturbations of sensor readings and calibrated parameters can be used to manipulate a system that employs optimal control. Hypergames form an extension of game theory that enables us to model strategic interactions where the players may have significantly different perceptions of the game(s) they are playing. Past work with hypergames has focused on relatively simple interactions consisting of a small set of discrete choices for each player. Here, we apply single-stage hypergames to larger systems with continuous variables. We find that manipulating constraints can be a more effective attacker strategy than manipulating objective function parameters. Moreover, the attacker need not change the underlying system to carry out a successful attack—it may be sufficient to deceive the defender controlling the system. It is possible to scale our approach up to even larger systems, but this will depend on the characteristics of the system in question, and we identify several characteristics that will make those systems amenable to hypergame analysis.

Soft errors caused by transient bit flips have the potential to significantly impact an application's behavior. This has motivated the design of an array of techniques to detect, isolate, and correct soft errors using microarchitectural, architectural, compilation-based, or application-level techniques to minimize their impact on the executing application. The first step toward the design of good error detection/correction techniques involves an understanding of an application's vulnerability to soft errors. In this paper, we present the first comprehensive characterization of the impact of soft errors on the convergence characteristics of six iterative methods using application-level fault injection. In particular, we consider the use of iterative methods to incrementally solve a linear system of equations, which constitute the core kernel in many scientific applications. We analyze the impact of soft errors in terms of the type of error (single-vs multi-bit), the distribution and location of bits affected, the data structure and statement impacted, and variation with time. In addition to understanding the vulnerability of iterative solvers to soft errors, this characterization can aid the design of fault injection campaigns that ensure systematic coverage.

BACKGROUND: To study a biological phenomenon such as finding mechanism of disease, common methodology is to generate the microarray data in different relevant conditions and find groups of genes co-expressed across conditions from such data. These groups might enable us to find biological processes involved in a disease condition. However, more detailed understanding can be made when information of a biological process associated with a particular condition is obtained from the data. Many algorithms are available which finds groups of co-expressed genes and associated conditions of co-expression that can help finding processes associated with particular condition. However, these algorithms depend on different input parameters for generating groups. For real datasets, it is difficult to use these algorithms due to unknown values of these parameters. RESULTS: We present here an algorithm, clustered groups, which finds groups of co-expressed genes and conditions of co-expression with minimal input from user. We used random datasets to derive a cutoff on the basis of which we filtered the resultant groups and showed that this can improve the relevance of obtained groups. We showed that the proposed algorithm performs better than other known algorithms on both real and synthetic datasets. We have also shown its application on a temporal microarray dataset by extracting biclusters and biological information hidden in those biclusters. CONCLUSIONS: Clustered groups is an algorithm which finds groups of co-expressed genes and conditions of co-expression using only a single parameter. We have shown that it works better than other existing algorithms. It can be used to find these groups in different data types such as microarray, proteomics, metabolomics etc.