A Call to Action: The New Academy of Food Law & Policy

The food system is affected by unique and complex laws. These laws call for a new generation of legal practitioners and scholars. This essay announces the creation of the Academy of Food Law and Policy. The Academy creates a network of law professors researching, teaching, and mentoring in food law and policy

Immune- and nonimmune-compartment-specific interferon responses are critical determinants of herpes simplex virus-induced generalized infections and acute liver failure

The interferon (IFN) response to viral pathogens is critical for host survival. In humans and mouse models, defects in IFN responses can result in lethal herpes simplex virus 1 (HSV-1) infections, usually from encephalitis. Although rare, HSV-1 can also cause fulminant hepatic failure, which is often fatal. Although herpes simplex encephalitis has been extensively studied, HSV-1 generalized infections and subsequent acute liver failure are less well understood. We previously demonstrated that IFN-αβγR-/- mice are exquisitely susceptible to liver infection following corneal infection with HSV-1. In this study, we used bone marrow chimeras of IFN-αβγR-/- (AG129) and wild-type (WT; 129SvEv) mice to probe the underlying IFN-dependent mechanisms that control HSV-1 pathogenesis. After infection, WT mice with either IFN-αβγR-/- or WT marrow exhibited comparable survival, while IFN-αβγR-/- mice with WT marrow had a significant survival advantage over their counterparts with IFN-αβγR-/- marrow. Furthermore, using bioluminescent imaging to maximize data acquisition, we showed that the transfer of IFN-competent hematopoietic cells controlled HSV-1 replication and damage in the livers of IFN-αβγR-/- mice. Consistent with this, the inability of IFN-αβγR-/- immune cells to control liver infection in IFN-αβγR-/- mice manifested as profoundly elevated aspartate transaminase (AST) and alanine transaminase (ALT) levels, indicative of severe liver damage. In contrast, IFN-αβγR-/-mice receiving WT marrow exhibited only modest elevations of AST and ALT levels. These studies indicate that IFN responsiveness of the immune system is a major determinant of viral tropism and damage during visceral HSV infections

Photon Blockade in the Ultrastrong Coupling Regime

We explore photon coincidence counting statistics in the ultrastrong-coupling regime where the atom-cavity coupling rate becomes comparable to the cavity resonance frequency. In this regime usual normal order correlation functions fail to describe the output photon statistics. By expressing the electric-field operator in the cavity-emitter dressed basis we are able to propose correlation functions that are valid for arbitrary degrees of light-matter interaction. Our results show that the standard photon blockade scenario is significantly modified for ultrastrong coupling. We observe parametric processes even for two-level emitters and temporal oscillations of intensity correlation functions at a frequency given by the ultrastrong photon emitter coupling. These effects can be traced back to the presence of two-photon cascade decays induced by counter-rotating interaction terms.Comment: minor revisions, supplementary information added, accepted for publication in PR

Role of the DNA Sensor STING in Protection from Lethal Infection following Corneal and Intracerebral Challenge with Herpes Simplex Virus 1

STING is a protein in the cytosolic DNA and cyclic dinucleotide sensor pathway that is critical for the initiation of innate responses to infection by various pathogens. Consistent with this, herpes simplex virus 1 (HSV-1) causes invariable and rapid lethality in STING-deficient (STING(-/-)) mice following intravenous (i.v.) infection. In this study, using real-time bioluminescence imaging and virological assays, as expected, we demonstrated that STING(-/-) mice support greater replication and spread in ocular tissues and the nervous system. In contrast, they did not succumb to challenge via the corneal route even with high titers of a virus that was routinely lethal to STING(-/-) mice by the i.v. route. Corneally infected STING(-/-) mice also showed increased periocular disease and increased corneal and trigeminal ganglia titers, although there was no difference in brain titers. They also showed elevated expression of tumor necrosis factor alpha (TNF-α) and CXCL9 relative to control mice but surprisingly modest changes in type I interferon expression. Finally, we also showed that HSV strains lacking the ability to counter autophagy and the PKR-driven antiviral state had near-wild-type virulence following intracerebral infection of STING(-/-) mice. Together, these data show that while STING is an important component of host resistance to HSV in the cornea, its previously shown immutable role in mediating host survival by the i.v. route was not recapitulated following a mucosal infection route. Furthermore, our data are consistent with the idea that HSV counters STING-mediated induction of the antiviral state and autophagy response, both of which are critical factors for survival following direct infection of the nervous system

Improved jet noise predictions in subsonic flows using an approximate composite asymptotic expansion of the adjoint Green's function in Goldstein's analogy

Our recent work on jet noise modeling (Afsar et al. 2019, PhilTrans. A., vol. 377) has confirmed that non-parallel flow effects are needed to determine the wave propagation aspect of the jet noise problem. The acoustic spectrum calculated using an asymptotic representation of non-parallel flow effects produces the correct spectral shape of the small angle radiation beyond that which can be predicted using a parallel (i.e. non-spreading) mean flow approximation to determine the wave propagation tensor in Goldstein’s generalized acoustic analogy formulation. While the peak noise predicted using this approach works remarkably well at low frequencies (up to and slightly beyond the peak Strouhal number), the high frequency prediction in Afsar et al. (2019) relied upon an ad-hoc composite asymptotic formula for the propagator that was also restricted to the small angle spectra. In this paper we therefore attempt to remedy this defect by using the O(1) frequency locally parallel flow Green’s function as a kind-of outer solution to the propagator tensor in which the non-parallel flow theory used in the latter reference acts as the ’inner’ solution that is valid at low frequencies and is transcendentally small beyond the peak frequency. The hope is that this approach will allow more robust high frequency predictions with a single set of turbulence parameters for the acoustic spectrum at any given acoustic Mach number. In other words, both non-parallel and locally parallel regions of the propagator tensor solution are multiplied by the same turbulence source structure in the acoustic spectrum integral. The paper highlights the basic formalism of the low frequency jet noise theory and sum- marises the technical problems and strategy we use to extend this approach to higher frequen- cies

Networks of nonlinear superconducting transmission line resonators

We investigate a network of coupled superconducting transmission line resonators, each of them made nonlinear with a capacitively shunted Josephson junction coupling to the odd flux modes of the resonator. The resulting eigenmode spectrum shows anticrossings between the plasma mode of the shunted junction and the odd resonator modes. Notably, we find that the combined device can inherit the complete nonlinearity of the junction, allowing for a description as a harmonic oscillator with a Kerr nonlinearity. Using a dc SQUID instead of a single junction, the nonlinearity can be tuned between 10 kHz and 4 MHz while maintaining resonance frequencies of a few gigahertz for realistic device parameters. An array of such nonlinear resonators can be considered a scalable superconducting quantum simulator for a Bose-Hubbard Hamiltonian. The device would be capable of accessing the strongly correlated regime and be particularly well suited for investigating quantum many-body dynamics of interacting particles under the influence of drive and dissipation.Comment: 18 pages, 3 figure

Dendritic Cell Autophagy Contributes to Herpes Simplex Virus-Driven Stromal Keratitis and Immunopathology

Herpetic stromal keratitis (HSK) is a blinding ocular disease that is initiated by HSV-1 and characterized by chronic inflammation in the cornea. Although HSK immunopathology of the cornea is well documented in animal models, events preceding this abnormal inflammatory cascade are poorly understood. In this study, we have examined the activation of pathological CD4T cells in the development of HSK. Dendritic cell autophagy (DC-autophagy) is an important pathway regulating ma- jor histocompatibility complex class II (MHCII)-dependent antigen presentation and proper CD4T cell activation during infectious diseases. Using DC-autophagy-deficient mice, we found that DC-autophagy significantly and specifically contributes to HSK disease without impacting early innate immune infiltration, viral clearance, or host survival. Instead, the observed phe- notype was attributable to the abrogated activation of CD4T cells and reduced inflammation in HSK lesions. We conclude that DC-autophagy is an important contributor to primary HSK immunopathology upstream of CD4T cell activation. IMPORTANCE Herpetic stromal keratitis (HSK) is the leading cause of infectious blindness in the United States and a rising cause worldwide. HSK is induced by herpes simplex virus 1 but is considered a disease of inappropriately sustained inflammation driven by CD4T cells. In this study, we investigated whether pathways preceding CD4T cell activation affect disease outcome. We found that autophagy in dendritic cells significantly contributed to the incidence of HSK. Dendritic cell autophagy did not alter immune control of the virus or neurological disease but specifically augmented CD4T cell activation and pathological corneal inflammation. This study broadens our understanding of the immunopathology that drives HSK and implicates the autophagy pathway as a new target for therapeutic intervention against this incurable form of infectious blindness

The Differential Interferon Responses of Two Strains of Stat1-Deficient Mice Do Not Alter Susceptibility to HSV-1 and VSV In Vivo

Stat1 is a pivotal transcription factor for generation of the interferon (IFN)-dependent antiviral response. Two Stat1 knockout mouse lines have been previously generated, one deleted the N-terminal domain (ΔNTD) and one in the DNA-binding domain (ΔDBD). These widely-used strains are assumed interchangeable, and both are highly susceptible to various pathogens. In this study, primary cells derived from ΔNTD mice were shown to be significantly more responsive to IFN, and established an antiviral state with greater efficiency than cells derived from ΔDBD mice, following infection with vesicular stomatitis virus and herpes simplex virus type-1. Also, while mice from both strains succumbed rapidly and equally to virus infection, ΔDBD mice supported significantly higher replication in brains and livers than ΔNTD mice. Endpoint-type experimental comparisons of these mouse strains are therefore misleading in failing to indicate important differences in virus replication and innate response