Recurrent Herpetic Stromal Keratitis in Mice: A Model for Studying Human HSK

Herpes simplex virus 1 (HSV-1) infection of the cornea leads to a potentially blinding disease, termed herpetic stromal keratitis (HSK) that is characterized by lesions of an immunoinflammatory nature. In spite of the fact that HSK typically presents as a recurrent disease due to reactivation of virus which latently infects the trigeminal ganglia, most murine studies of HSK have employed a primary and not recurrent model of the disease. This report documents the several recurrent models of HSK that have been developed and how data generated from these models differs in some important aspects from data generated following primary infection of the cornea. Chief among these differences is the fact that recurrent HSK takes place in the context of an animal that has a preexisting anti-HSV immune response, while primary HSK occurs in an animal that is developing such a response. We will document both differences and similarities that derive from this fundamental difference in these models with an eye towards possible vaccines and therapies that demonstrate promise in treating HSK

Herpes simplex keratitis: Challenges in diagnosis and clinical management

Herpes simplex virus is responsible for numerous ocular diseases, the most common of which is herpetic stromal keratitis. This is a recurrent infection of the cornea that typically begins with a subclinical infection of the cornea that establishes a latent infection of sensory ganglia, most often the trigeminal ganglia. Recurring infections occur when the virus is reactivated from latency and travels back to the cornea, where it restimulates an inflammatory response. This inflammatory response can lead to decreased corneal sensation, scarring, and blindness. The diagnosis of these lesions as the result of a recurrent herpes simplex virus infection can at times be problematic. Currently, herpetic stromal keratitis is diagnosed by its clinical presentation on the slit-lamp examination, but the literature does not always support the accuracy of these clinical findings. Other diagnostic tests such as polymerase chain reaction assay, enzyme-linked immunosorbent assay, immunofluorescent antibody, and viral cultures have provided more definitive diagnosis, but also have some limitations. That said, accurate diagnosis is necessary for proper treatment, in order to prevent serious consequences. Current treatment reduces the severity of lesions and controls further viral spread, but does not provide a cure

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

Demonstration of fast-acting protection as a key enabler for more-electric aircraft interconnected architetctures

Driven by anticipated fuel-burn and efficiency benefits, the more-electric aircraft (MEA) concept is a technological shift in the aviation industry, which seeks to replace mechanical, hydraulic and pneumatic functions with electrical equivalents. This shift has greatly increased the electrical power demands of aircraft and has made MEA networks larger and more complex. Consequently, new and more efficient electrical architectures are required, with interconnected generation potentially being one design approach that could bring improved performance and fuel savings. This study discusses the current state of interconnected generation in the aviation industry and key technological advances that could facilitate feasible interconnection options. This study demonstrates that interconnected systems can breach certification rules under fault conditions. Through modelling and simulation, it investigates the airworthiness-requirements compliance of potential impedance solutions to this issue and quantifies the potential impact on system weight. It concludes by identifying fast fault clearing protection as being a key enabling technology that facilitates the use of light-weight and standards-compliant architectures

Evaluation of the impact of high bandwidth energy storage systems on DC protection

The integration of high bandwidth energy storage systems (ESS) in compact DC electrical power systems can increase the operational capability and overall flexibility of the network. However, the impact of ESSs on the performance of existing DC protection systems is not well understood. This paper identifies the key characteristics of the ESS that determine the extent of the protection blinding effects on slower acting generator systems on the network. It shows that higher fault impedances beyond that of an evaluated critical level will dampen the response of slower acting generator systems, decreasing the speed of corresponding overcurrent protection operation. The paper demonstrates the limitations of existing protection solutions and identifies more suitable protection approaches to remove/minimize the effects of protection blinding

Comparison of candidate architectures for future distributed propulsion aircraft

Turbine engine driven distributed electrical aircraft power systems (also referred to as Turboelectric Distributed Propulsion (TeDP)) are proposed for providing thrust for future aircraft with superconducting components operating at 77K in order for performance and emissions targets to be met. The proposal of such systems presents a radical change from current state-of-the-art aero-electrical power systems. Central to the development of such power systems are architecture design trades which must consider system functionality and performance, system robustness and fault ride-through capability, in addition to the balance between mass and efficiency. This paper presents a quantitative comparison of the three potential candidate architectures for TeDP electrical networks. This analysis provides the foundations for establishing the feasibility of these different architectures subject to design and operational constraints. The findings of this paper conclude that a purely AC synchronous network performs best in terms of mass and efficiency, but similar levels of functionality and controllability to an architecture with electrical decoupling via DC cannot readily be achieved. If power electronic converters with cryocoolers are found to be necessary for functionality and controllability purposes, then studies show that a significant increase in the efficiency of solid state switching components is necessary to achieve specified aircraft performance targets

Development of voltage standards for turbo-electric distributed propulsion aircraft power systems

Distributed propulsion is being considered as a possible solution to increase aircraft efficiency, reduce fuel costs and reduce emissions. The size, weight and efficiency of components within a Turbo-electric Distributed Propulsion (TeDP) system are dependent on the voltage level of the electrical power network. Current aircraft voltage standards do not address the architecture of distributed propulsion and so a review of voltage standards from different industries is conducted with areas of commonality addressed. An example of TeDP architecture is presented and analyzed to highlight how current aircraft standards may not apply to TeDP. A summary of challenges in developing standards for a TeDP is compiled with a stakeholder analysis to demonstrate the wide range of industries and personnel with vested interests in the development of voltage standards and recommended practices for TeDP

Pseudoalteromonas piratica sp. nov., a budding, prosthecate bacterium from diseased Montipora capitata, and emended description of the genus Pseudoalteromonas

A Gram-stain-negative, motile, rod-shaped bacterium designated OCN003T was cultivated from mucus taken from a diseased colony of the coral Montipora capitata in Kāne‘ohe Bay, O‘ahu, Hawai‘i. Colonies of OCN003T were pale yellow, 1–3 mm in diameter, convex, smooth and entire. The strain was heterotrophic, strictly aerobic and strictly halophilic. Cells of OCN003T produced buds on peritrichous prosthecae. Growth occurred within the pH range of 5.5 to 10, and the temperature range of 14 to 39 °C. Major fatty acids were 16 : 1!7c, 16 : 0, 18 : 1!7c, 17 : 1!8c, 12 : 0 3-OH and 17 : 0. Phylogenetic analysis of 1399 nucleotides of the 16S rRNA gene nucleotide sequence and a multi-locus sequence analysis of three genes placed OCN003T in the genus Pseudoalteromonas and indicated that the nearest relatives described are Pseudoalteromonas spongiae, P. luteoviolacea, P. ruthenica and P. phenolica (97–99 % sequence identity). The DNA G+C content of the strain’s genome was 40.0 mol%. Based on in silico DNA–DNA hybridization and phenotypic differences from related type strains, we propose that OCN003T represents the type strain of a novel species in the genus Pseudoalteromonas, proposed as Pseudoalteromonas piratica sp. nov. OCN003T (=CCOS1042T =CIP 111189T ). An emended description of the genus Pseudoalteromonas is presented

Synthesis of cyclic alpha-diazo-beta-keto sulfoxides in batch and continuous flow

Diazo transfer to beta–keto sulfoxides to form stable isolable alpha-diazo-beta-keto sulfoxides has been achieved for the first time. Both monocyclic and benzofused ketone derived beta-keto sulfoxides were successfully explored as substrates for diazo transfer. Use of continuous flow leads to isolation of the desired compounds in enhanced yields relative to standard batch conditions, with short reaction times, increased safety profile and potential to scale up