Regulating the adaptive immune response to respiratory virus infection

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Recent years have seen several advances in our understanding of immunity to virus infection of the lower respiratory tract, including to influenza virus infection. Here, we review the cellular targets of viruses and the features of the host immune response that are unique to the lungs. We describe the interplay between innate and adaptive immune cells in the induction, expression and control of antiviral immunity, and discuss the impact of the infected lung milieu on moulding the response of antiviral effector T cells. Recent findings on the mechanisms that underlie the increased frequency of severe pulmonary bacterial infections following respiratory virus infection are also discussed

Fast algorithms for large scale generalized distance weighted discrimination

High dimension low sample size statistical analysis is important in a wide range of applications. In such situations, the highly appealing discrimination method, support vector machine, can be improved to alleviate data piling at the margin. This leads naturally to the development of distance weighted discrimination (DWD), which can be modeled as a second-order cone programming problem and solved by interior-point methods when the scale (in sample size and feature dimension) of the data is moderate. Here, we design a scalable and robust algorithm for solving large scale generalized DWD problems. Numerical experiments on real data sets from the UCI repository demonstrate that our algorithm is highly efficient in solving large scale problems, and sometimes even more efficient than the highly optimized LIBLINEAR and LIBSVM for solving the corresponding SVM problems

T Cell Responses during Acute Respiratory Virus Infection

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.The T cell response is an integral and essential part of the host immune response to acute virus infection. Each viral pathogen has unique, frequently nuanced, aspects to its replication, which affects the host response and as a consequence the capacity of the virus to produce disease. There are, however, common features to the T cell response to viruses, which produce acute limited infection. This is true whether virus replication is restricted to a single site, for example, the respiratory tract (RT), CNS etc., or replication is in multiple sites throughout the body. In describing below the acute T cell response to virus infection, we employ acute virus infection of the RT as a convenient model to explore this process of virus infection and the host response. We divide the process into three phases: the induction (initiation) of the response, the expression of antiviral effector activity resulting in virus elimination, and the resolution of inflammation with restoration of tissue homeostasis

The phosphoinositide 3-kinase-dependent activation of Btk is required for optimal eicosanoid production and generation of reactive oxygen species in antigen-stimulated mast cells

Activated mast cells are a major source of the eicosanoids PGD(2) and leukotriene C(4) (LTC(4)), which contribute to allergic responses. These eicosanoids are produced following the ERK1/2-dependent activation of cytosolic phospholipase A(2), thus liberating arachidonic acid, which is subsequently metabolized by the actions of 5-lipoxygenase and cyclooxygenase to form LTC(4) and PGD(2), respectively. These pathways also generate reactive oxygen species (ROS), which have been proposed to contribute to FcepsilonRI-mediated signaling in mast cells. In this study, we demonstrate that, in addition to ERK1/2-dependent pathways, ERK1/2-independent pathways also regulate FcepsilonRI-mediated eicosanoid and ROS production in mast cells. A role for the Tec kinase Btk in the ERK1/2-independent regulatory pathway was revealed by the significantly attenuated FcepsilonRI-dependent PGD(2), LTC(4), and ROS production in bone marrow-derived mast cells of Btk(-/-) mice. The FcepsilonRI-dependent activation of Btk and eicosanoid and ROS generation in bone marrow-derived mast cells and human mast cells were similarly blocked by the PI3K inhibitors, Wortmannin and LY294002, indicating that Btk-regulated eicosanoid and ROS production occurs downstream of PI3K. In contrast to ERK1/2, the PI3K/Btk pathway does not regulate cytosolic phospholipase A(2) phosphorylation but rather appears to regulate the generation of ROS, LTC(4), and PGD(2) by contributing to the necessary Ca(2+) signal for the production of these molecules. These data demonstrate that strategies to decrease mast cell production of ROS and eicosanoids would have to target both ERK1/2- and PI3K/Btk-dependent pathways

Maximizing Welfare in Social Networks under a Utility Driven Influence Diffusion Model

Motivated by applications such as viral marketing, the problem of influence maximization (IM) has been extensively studied in the literature. The goal is to select a small number of users to adopt an item such that it results in a large cascade of adoptions by others. Existing works have three key limitations. (1) They do not account for economic considerations of a user in buying/adopting items. (2) Most studies on multiple items focus on competition, with complementary items receiving limited attention. (3) For the network owner, maximizing social welfare is important to ensure customer loyalty, which is not addressed in prior work in the IM literature. In this paper, we address all three limitations and propose a novel model called UIC that combines utility-driven item adoption with influence propagation over networks. Focusing on the mutually complementary setting, we formulate the problem of social welfare maximization in this novel setting. We show that while the objective function is neither submodular nor supermodular, surprisingly a simple greedy allocation algorithm achieves a factor of $(1-1/e-\epsilon)$ of the optimum expected social welfare. We develop \textsf{bundleGRD}, a scalable version of this approximation algorithm, and demonstrate, with comprehensive experiments on real and synthetic datasets, that it significantly outperforms all baselines.Comment: 33 page

Quantum super-cavity with atomic mirrors

We study single-photon transport in an array of coupled microcavities where two two-level atomic systems are embedded in two separate cavities of the array. We find that a single-photon can be totally reflected by a single two-level system. However, two separate two-level systems can also create, between them, single-photon quasi-bound states. Therefore, a single two-level system in the cavity array can act as a mirror while a different type of cavity can be formed by using two two-level systems, acting as tunable "mirrors", inside two separate cavities in the array. In analogy with superlattices in solid state, we call this new "cavity inside a coupled-cavity array" a super-cavity. This supercavity is the quantum analog of Fabry-Perot interferometers. Moreover, we show that the physical properties of this quantum super-cavity can be adjusted by changing the frequencies of these two-level systems.Comment: 13 pages, 9 figure

Photoinjector-generation of a flat electron beam with transverse emittance ratio of 100

The generation of a flat electron beam directly from a photoinjector is an attractive alternative to the electron damping ring as envisioned for linear colliders. It also has potential applications to light sources such as the generation of ultra-short x-ray pulses or Smith-Purcell free electron lasers. In this Letter, we report on the experimental generation of a flat-beam with a measured transverse emittance ratio of $100\pm 20.2$ for a bunch charge of $\sim 0.5$ nC; the smaller measured normalized root-mean-square emittance is $\sim 0.4$ $\mu$m and is limited by the resolution of our experimental setup. The experimental data, obtained at the Fermilab/NICADD Photoinjector Laboratory, are compared with numerical simulations and the expected scaling laws.Comment: 5 pages, 3 figure