skip to main content

Search for: All records

Creators/Authors contains: "Roy, D."

Note: When clicking on a Digital Object Identifier (DOI) number, you will be taken to an external site maintained by the publisher. Some full text articles may not yet be available without a charge during the embargo (administrative interval).
What is a DOI Number?

Some links on this page may take you to non-federal websites. Their policies may differ from this site.

  1. Abstract Molecular interactions are studied as independent networks in systems biology. However, molecular networks do not exist independently of each other. In a network of networks approach (called multiplex), we study the joint organization of transcriptional regulatory network (TRN) and protein–protein interaction (PPI) network. We find that TRN and PPI are non-randomly coupled across five different eukaryotic species. Gene degrees in TRN (number of downstream genes) are positively correlated with protein degrees in PPI (number of interacting protein partners). Gene–gene and protein–protein interactions in TRN and PPI, respectively, also non-randomly overlap. These design principles are conserved across the five eukaryoticmore »species. Robustness of the TRN–PPI multiplex is dependent on this coupling. Functionally important genes and proteins, such as essential, disease-related and those interacting with pathogen proteins, are preferentially situated in important parts of the human multiplex with highly overlapping interactions. We unveil the multiplex architecture of TRN and PPI. Multiplex architecture may thus define a general framework for studying molecular networks. This approach may uncover the building blocks of the hierarchical organization of molecular interactions.« less
    Free, publicly-accessible full text available December 1, 2022
  2. A source node forwards fresh status updates as a point process to a network of observer nodes. Within the network of observers, these updates are forwarded as point processes from node to node. Each node wishes its knowledge of the source to be as timely as possible. In this network, timeliness at each node is measured by an age of information metric: how old is the timestamp of the freshest received update. This work extends a method for evaluating the average age at each node in the network when nodes forward updates using a memoryless gossip protocol. This method ismore »then demonstrated by age analysis for a simple network.« less
    Free, publicly-accessible full text available September 27, 2022
  3. A source node updates its status as a point process and also forwards its updates to a network of observer nodes. Within the network of observers, these updates are forwarded as point processes from node to node. Each node wishes its knowledge of the source to be as timely as possible. In this network, timeliness is measured by a discrete form of age of information: each status change at the source is referred to as a version and the age at a node is how many versions out of date is its most recent update from the source. This workmore »introduces a method for evaluating the average version age at each node in the network when nodes forward updates using a memoryless gossip protocol. This method is then demonstrated by version age analysis for a collection of simple networks. For gossip on a complete graph with symmetric updating rates, it is shown that each node has average age that grows as the logarithm of the network size.« less
    Free, publicly-accessible full text available July 12, 2022
  4. We quantify, over inter-continental paths, the ageing of TCP packets, throughput and delay for different TCP congestion control algorithms containing a mix of loss-based, delay-based and hybrid congestion control algorithms. In comparing these TCP variants to ACP+, an improvement over ACP, we shed better light on the ability of ACP+ to deliver timely updates over fat pipes and long paths. ACP+ estimates the network conditions on the end-to-end path and adapts the rate of status updates to minimize age. It achieves similar average age as the best (age wise) performing TCP algorithm but at end-to-end throughputs that are two ordersmore »of magnitude smaller. We also quantify the significant improvements that ACP+ brings to age control over a shared multiaccess channel.« less
  5. Free, publicly-accessible full text available August 1, 2022
  6. We consider updating strategies for a local cache which downloads time-sensitive files from a remote server through a bandwidth-constrained link. The files are requested randomly from the cache by local users according to a popularity distribution which varies over time according to a Markov chain structure. We measure the freshness of the requested time-sensitive files through their Age of Information (AoI). The goal is then to minimize the average AoI of all requested files by appropriately designing the local cache’s downloading strategy. To achieve this goal, the original problem is relaxed and cast into a Constrained Markov Decision Problem (CMDP),more »which we solve using a Lagrangian approach and Linear Programming. Inspired by this solution for the relaxed problem, we propose a practical cache updating strategy that meets all the constraints of the original problem. Under certain assumptions, the practical updating strategy is shown to be optimal for the original problem in the asymptotic regime of a large number of files. For a finite number of files, we show the gain of our practical updating strategy over the traditional square-root-law strategy (which is optimal for fixed non time-varying file popularities) through numerical simulations.« less
  7. Upon infection of its host cell, human immunodeficiency virus (HIV) establishes a quiescent and non-productive state capable of spontaneous reactivation. Diverse cell types harboring the provirus form a latent reservoir, constituting a major obstacle to curing HIV. Here, we investigate the effects of latency reversal agents (LRAs) in an HIV-infected THP-1 monocyte cell line in vitro. We demonstrate that leading drug treatments synergize activation of the HIV long terminal repeat (LTR) promoter. We establish a latency model in THP-1 monocytes using a replication incompetent HIV reporter vector with functional Tat, and show that chromatin modifiers synergize with a potent transcriptionalmore »activator to enhance HIV reactivation, similar to T-cells. Furthermore, leading reactivation cocktails are shown to differentially affect latency reactivation and surface expression of chemokine receptor type 4 (CXCR4), leading to altered host cell migration. This study investigates the effect of chromatin-modifying LRA treatments on HIV latent reactivation and cell migration in monocytes. As previously reported in T-cells, epigenetic mechanisms in monocytes contribute to controlling the relationship between latent reactivation and cell migration. Ultimately, advanced “Shock and Kill” therapy needs to successfully target and account for all host cell types represented in a complex and composite latency milieu.« less
    Free, publicly-accessible full text available June 1, 2022
  8. Upon treatment removal, spontaneous reactivation of latently infected T cells remains a major barrier toward curing HIV. Therapies that reactivate and clear the latent reservoir are only partially effective, while latency-promoting agents (LPAs) used to suppress reactivation and stabilize latency are understudied and lack diversity in their mechanisms of action. Here, we identify additional LPAs using a screen for gene-expression fluctuations (or “noise”) that drive cell-fate specification and control HIV reactivation from latency. Single-cell protein dynamics of a minimal HIV gene circuit were monitored with time-lapse fluorescence microscopy. We screened 1,806 drugs, out of which 279 modulate noise magnitude ormore »half autocorrelation time. Next, we tested the strongest noise modulators in a Jurkat T cell latency model and discovered three LPAs that would be overlooked by quantifying their mean expression levels alone. The LPAs reduced reactivation of latency in both Jurkat and primary cell models when challenged by synergistic and potent combinations of HIV activators. The two strongest LPAs, NSC 401005 and NSC 400938, are structurally and functionally related to inhibitors of thioredoxin reductase, a protein involved in maintaining redox balance in host cells. Experiments with multiple functional analogs revealed two additional LPAs, PX12 and tiopronin, and suggest a potential LPA family, within which some are commercially available and Food and Drug Administration–approved. The LPAs presented here may provide new strategies to complement antiretroviral treatments. Screening for gene expression noise holds the potential for drug discovery in other diseases.« less