How to avoid a local epidemic becoming a global pandemic

Here, we combine international air travel passenger data with a standard epidemiological model of the initial 3 mo of the COVID-19 pandemic (January through March 2020; toward the end of which the entire world locked down). Using the information available during this initial phase of the pandemic, our model accurately describes the main features of the actual global development of the pandemic demonstrated by the high degree of coherence between the model and global data. The validated model allows for an exploration of alternative policy efficacies (reducing air travel and/or introducing different degrees of compulsory immigration quarantine upon arrival to a country) in delaying the global spread of SARS-CoV-2 and thus is suggestive of similar efficacy in anticipating the spread of future global disease outbreaks. We show that a lesson from the recent pandemic is that reducing air travel globally is more effective in reducing the global spread than adopting immigration quarantine. Reducing air travel out of a source country has the most important effect regarding the spreading of the disease to the rest of the world. Based upon our results, we propose a digital twin as a further developed tool to inform future pandemic decision-making to inform measures intended to control the spread of disease agents of potential future pandemics. We discuss the design criteria for such a digital twin model as well as the feasibility of obtaining access to the necessary online data on international air travel

Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses.

Mesenchymal tumor subpopulations secrete pro-tumorigenic cytokines and promote treatment resistance1-4. This phenomenon has been implicated in chemorefractory small cell lung cancer and resistance to targeted therapies5-8, but remains incompletely defined. Here, we identify a subclass of endogenous retroviruses (ERVs) that engages innate immune signaling in these cells. Stimulated 3 prime antisense retroviral coding sequences (SPARCS) are oriented inversely in 3' untranslated regions of specific genes enriched for regulation by STAT1 and EZH2. Derepression of these loci results in double-stranded RNA generation following IFN-γ exposure due to bi-directional transcription from the STAT1-activated gene promoter and the 5' long terminal repeat of the antisense ERV. Engagement of MAVS and STING activates downstream TBK1, IRF3, and STAT1 signaling, sustaining a positive feedback loop. SPARCS induction in human tumors is tightly associated with major histocompatibility complex class 1 expression, mesenchymal markers, and downregulation of chromatin modifying enzymes, including EZH2. Analysis of cell lines with high inducible SPARCS expression reveals strong association with an AXL/MET-positive mesenchymal cell state. While SPARCS-high tumors are immune infiltrated, they also exhibit multiple features of an immune-suppressed microenviroment. Together, these data unveil a subclass of ERVs whose derepression triggers pathologic innate immune signaling in cancer, with important implications for cancer immunotherapy

Functional Assessment of EnvZ/OmpR Two-Component System in Shewanella oneidensis

EnvZ and OmpR constitute the bacterial two-component signal transduction system known to mediate osmotic stress response in a number of Gram-negative bacteria. In an effort to understand the mechanism through which Shewanella oneidensis senses and responds to environmental osmolarity changes, structure of the ompR-envZ operon was determined with Northern blotting assay and roles of the EnvZ/OmpR two-component system in response to various stresses were investigated with mutational analysis, quantitative reverse transcriptase PCR (qRT-PCR), and phenotype microarrays. Results from the mutational analysis and qRT-PCR suggested that the EnvZ/OmpR system contributed to osmotic stress response of S. oneidensis and very likely engaged a similar strategy employed by E. coli, which involved reciprocal regulation of two major porin coding genes. Additionally, the ompR-envZ system was also found related to cell motility. We further showed that the ompR-envZ dependent regulation of porin genes and motility resided almost completely on ompR and only partially on envZ, indicating additional mechanisms for OmpR phosphorylation. In contrast to E. coli lacking ompR-envZ, however, growth of S. oneidensis did not show a significant dependence on ompR-envZ even under osmotic stress. Further analysis with phenotype microarrays revealed that the S. oneidensis strains lacking a complete ompR-envZ system displayed hypersensitivities to a number of agents, especially in alkaline environment. Taken together, our results suggest that the function of the ompR-envZ system in S. oneidensis, although still connected with osmoregulation, has diverged considerably from that of E. coli. Additional mechanism must exist to support growth of S. oneidensis under osmotic stress

Engineering of quantum dot photon sources via electro-elastic fields

The possibility to generate and manipulate non-classical light using the tools of mature semiconductor technology carries great promise for the implementation of quantum communication science. This is indeed one of the main driving forces behind ongoing research on the study of semiconductor quantum dots. Often referred to as artificial atoms, quantum dots can generate single and entangled photons on demand and, unlike their natural counterpart, can be easily integrated into well-established optoelectronic devices. However, the inherent random nature of the quantum dot growth processes results in a lack of control of their emission properties. This represents a major roadblock towards the exploitation of these quantum emitters in the foreseen applications. This chapter describes a novel class of quantum dot devices that uses the combined action of strain and electric fields to reshape the emission properties of single quantum dots. The resulting electro-elastic fields allow for control of emission and binding energies, charge states, and energy level splittings and are suitable to correct for the quantum dot structural asymmetries that usually prevent these semiconductor nanostructures from emitting polarization-entangled photons. Key experiments in this field are presented and future directions are discussed.Comment: to appear as a book chapter in a compilation "Engineering the Atom-Photon Interaction" published by Springer in 2015, edited by A. Predojevic and M. W. Mitchel

Integrating transposable elements in the 3D genome

Chromosome organisation is increasingly recognised as an essential component of genome regulation, cell fate and cell health. Within the realm of transposable elements (TEs) however, the spatial information of how genomes are folded is still only rarely integrated in experimental studies or accounted for in modelling. Whilst polymer physics is recognised as an important tool to understand the mechanisms of genome folding, in this commentary we discuss its potential applicability to aspects of TE biology. Based on recent works on the relationship between genome organisation and TE integration, we argue that existing polymer models may be extended to create a predictive framework for the study of TE integration patterns. We suggest that these models may offer orthogonal and generic insights into the integration profiles (or "topography") of TEs across organisms. In addition, we provide simple polymer physics arguments and preliminary molecular dynamics simulations of TEs inserting into heterogeneously flexible polymers. By considering this simple model, we show how polymer folding and local flexibility may generically affect TE integration patterns. The preliminary discussion reported in this commentary is aimed to lay the foundations for a large-scale analysis of TE integration dynamics and topography as a function of the three-dimensional host genome

Fundamental Concepts of Cyber Resilience: Introduction and Overview

Given the rapid evolution of threats to cyber systems, new management approaches are needed that address risk across all interdependent domains (i.e., physical, information, cognitive, and social) of cyber systems. Further, the traditional approach of hardening of cyber systems against identified threats has proven to be impossible. Therefore, in the same way that biological systems develop immunity as a way to respond to infections and other attacks, so too must cyber systems adapt to ever-changing threats that continue to attack vital system functions, and to bounce back from the effects of the attacks. Here, we explain the basic concepts of resilience in the context of systems, discuss related properties, and make business case of cyber resilience. We also offer a brief summary of ways to assess cyber resilience of a system, and approaches to improving cyber resilience.Comment: This is a preprint version of a chapter that appears in the book "Cyber Resilience of Systems and Networks," Springer 201

Wet Adhesion and Adhesive Locomotion of Snails on Anti-Adhesive Non-Wetting Surfaces

Creating surfaces capable of resisting liquid-mediated adhesion is extremely difficult due to the strong capillary forces that exist between surfaces. Land snails use this to adhere to and traverse across almost any type of solid surface of any orientation (horizontal, vertical or inverted), texture (smooth, rough or granular) or wetting property (hydrophilic or hydrophobic) via a layer of mucus. However, the wetting properties that enable snails to generate strong temporary attachment and the effectiveness of this adhesive locomotion on modern super-slippy superhydrophobic surfaces are unclear. Here we report that snail adhesion overcomes a wide range of these microscale and nanoscale topographically structured non-stick surfaces. For the one surface which we found to be snail resistant, we show that the effect is correlated with the wetting response of the surface to a weak surfactant. Our results elucidate some critical wetting factors for the design of anti-adhesive and bio-adhesion resistant surfaces

Founder populations and their uses for breast cancer genetics

Numerous founder mutations have been reported in BRCA1 and BRCA2. For genetic screening of a population with a founder mutation, testing can be targeted to the mutation, allowing for a more rapid and less expensive test. In addition, more precise estimates of the prior probability of carrying a mutation and of the likelihood of a mutation carrier developing cancer should be possible. For a given founder mutation a large number of carriers are available, so that focused scientific studies of penetrance, expression, and genetic and environmental modifiers of risk can be performed. Finally, founder populations may be a powerful resource to localize additional breast cancer susceptibility loci, because of the reduction in locus heterogeneity