Few-Mode Fiber Coupled Superconducting Nanowire Single-Photon Detectors for Photon Efficient Optical Communications

The NASA Glenn Research Center's development of a high-photon efficiency real-time optical communications ground receiver has added superconducting nanowire single-photon detectors (SNSPDs) coupled with few-mode fibers (FMF). High data rate space-to-ground optical communication links require enhanced ground receiver sensitivity to reduce spacecraft transmitter constraints, and therefore require highly efficient coupling from fiber to detector. In the presence of atmospheric turbulence the received optical wave front can be severely distorted introducing higher-order spatial mode components to the received signal. To reduce mode filtering and mismatch loss and the resulting degradations to detector coupling efficiency, we explore the use of few-mode fiber coupling to commercial single-pixel SNSPDs. Graded index 20-m few-mode fibers allow the commercial single pixel SNSPD's active area to couple with equal efficiency as single mode fibers. Here we determine detector characteristics such as count rate, detection efficiency, dark counts, and jitter, as well as detection efficiencies for higher-order fiber spatial modes. Additionally, we assess the laboratory performance of the detectors in an optical system which emulates future deep space optical communications links

Bell Inequality Experiment for a High Brightness Time-Energy Entangled Source

A periodically poled MgO - doped LiNbO3 (MgO:LN) non-degenerate photon pair source is utilized for spontaneous parametric down-conversion of 532-nanometer photons into time-energy entangled pairs of 800- and 1600-nanometer photons. The entangled photons are separated using previously detailed sorting optics, such that each wavelength is independently directed through one of two modified Mach-Zehnder interferometers - also known as a Franson interferometer - after which they are fiber-optically guided to high-efficiency photon detectors. Output from the detectors is sent to a high resolution time tagger, where coincidences between the entangled photons are recorded. By varying the length of the long path in one Mach-Zehnder interferometer, it is possible to observe high visibility sinusoidal fringes in the measured coincidence rates (while no variation is seen in single photon detection rates). These fringes - due to interference between the photon probability amplitudes - are indicative of a violation of the Bell inequality, and confirm inconsistencies with local hidden variable theory for the correlations of the time-energy entangled photon pairs

A Pharmacogenetic Approach to Identify Mutant Forms of α-Galactosidase A that Respond to a Pharmacological Chaperone for Fabry Disease

Fabry disease is caused by mutations in the gene (GLA) that encodes α-galactosidase A (α-Gal A). The iminosugar AT1001 (GR181413A, migalastat hydrochloride, 1-deoxygalactonojirimycin) is a pharmacological chaperone that selectively binds and stabilizes α-Gal A, increasing total cellular levels and activity for some mutant forms (defined as “responsive”). In this study, we developed a cell-based assay in cultured HEK-293 cells to identify mutant forms of α-Gal A that are responsive to AT1001. Concentration-dependent increases in α-Gal A activity in response to AT1001 were shown for 49 (60%) of 81 mutant forms. The responses of α-Gal A mutant forms were generally consistent with the responses observed in male Fabry patient-derived lymphoblasts. Importantly, the HEK-293 cell responses of 19 α-Gal A mutant forms to a clinically achievable concentration of AT1001 (10 µM) were generally consistent with observed increases in α-Gal A activity in peripheral blood mononuclear cells from male Fabry patients orally administered AT1001 during Phase 2 clinical studies. This indicates that the cell-based responses can identify mutant forms of α-Gal A that are likely to respond to AT1001 in vivo. Thus, the HEK-293 cell-based assay may be a useful aid in the identification of Fabry patients with AT1001-responsive mutant forms. Hum Mutat 32:1–13, 2011. © 2011 Wiley-Liss, Inc

The future of zoonotic risk prediction

In the light of the urgency raised by the COVID-19 pandemic, global investment in wildlife virology is likely to increase, and new surveillance programmes will identify hundreds of novel viruses that might someday pose a threat to humans. To support the extensive task of laboratory characterization, scientists may increasingly rely on data-driven rubrics or machine learning models that learn from known zoonoses to identify which animal pathogens could someday pose a threat to global health. We synthesize the findings of an interdisciplinary workshop on zoonotic risk technologies to answer the following questions. What are the prerequisites, in terms of open data, equity and interdisciplinary collaboration, to the development and application of those tools? What effect could the technology have on global health? Who would control that technology, who would have access to it and who would benefit from it? Would it improve pandemic prevention? Could it create new challenges? This article is part of the theme issue 'Infectious disease macroecology: parasite diversity and dynamics across the globe'.Peer reviewe

Using decision analysis to support proactive management of emerging infectious wildlife diseases

Despite calls for improved responses to emerging infectious diseases in wildlife, management is seldom considered until a disease has been detected in affected populations. Reactive approaches may limit the potential for control and increase total response costs. An alternative, proactive management framework can identify immediate actions that reduce future impacts even before a disease is detected, and plan subsequent actions that are conditional on disease emergence. We identify four main obstacles to developing proactive management strategies for the newly discovered salamander pathogen Batrachochytrium salamandrivorans (Bsal). Given that uncertainty is a hallmark of wildlife disease management and that associated decisions are often complicated by multiple competing objectives, we advocate using decision analysis to create and evaluate trade-offs between proactive (pre-emergence) and reactive (post-emergence) management options. Policy makers and natural resource agency personnel can apply principles from decision analysis to improve strategies for countering emerging infectious diseases

The validation of pharmacogenetics for the identification of Fabry patients to be treated with migalastat

PURPOSE: Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the α-galactosidase A gene. Migalastat, a pharmacological chaperone, binds to specific mutant forms of α-galactosidase A to restore lysosomal activity. METHODS: A pharmacogenetic assay was used to identify the α-galactosidase A mutant forms amenable to migalastat. Six hundred Fabry disease-causing mutations were expressed in HEK-293 (HEK) cells; increases in α-galactosidase A activity were measured by a good laboratory practice (GLP)-validated assay (GLP HEK/Migalastat Amenability Assay). The predictive value of the assay was assessed based on pharmacodynamic responses to migalastat in phase II and III clinical studies. RESULTS: Comparison of the GLP HEK assay results in in vivo white blood cell α-galactosidase A responses to migalastat in male patients showed high sensitivity, specificity, and positive and negative predictive values (≥0.875). GLP HEK assay results were also predictive of decreases in kidney globotriaosylceramide in males and plasma globotriaosylsphingosine in males and females. The clinical study subset of amenable mutations (n = 51) was representative of all 268 amenable mutations identified by the GLP HEK assay. CONCLUSION: The GLP HEK assay is a clinically validated method of identifying male and female Fabry patients for treatment with migalastat

Cytokine responses to the anti-schistosome vaccine candidate antigen glutathione-S-transferase vary with host age and are boosted by praziquantel treatment.

BACKGROUND: Improved helminth control is required to alleviate the global burden of schistosomiasis and schistosome-associated pathologies. Current control efforts rely on the anti-helminthic drug praziquantel (PZQ), which enhances immune responses to crude schistosome antigens but does not prevent re-infection. An anti-schistosome vaccine based on Schistosoma haematobium glutathione-S-transferase (GST) is currently in Phase III clinical trials, but little is known about the immune responses directed against this antigen in humans naturally exposed to schistosomes or how these responses change following PZQ treatment. METHODOLOGY: Blood samples from inhabitants of a Schistosoma haematobium-endemic area were incubated for 48 hours with or without GST before (n = 195) and six weeks after PZQ treatment (n = 107). Concentrations of cytokines associated with innate inflammatory (TNFα, IL-6, IL-8), type 1 (Th1; IFNγ, IL-2, IL-12p70), type 2 (IL-4, IL-5, IL-13), type 17 (IL-17A, IL-21, IL-23p19) and regulatory (IL-10) responses were quantified in culture supernatants via enzyme-linked immunosorbent assay (ELISA). Factor analysis and multidimensional scaling were used to analyse multiple cytokines simultaneously. PRINCIPAL FINDINGS: A combination of GST-specific type 2 (IL-5 and IL-13) and regulatory (IL-10) cytokines was significantly lower in 10-12 year olds, the age group at which S. haematobium infection intensity and prevalence peak, than in 4-9 or 13+ year olds. Following PZQ treatment there was an increase in the number of participants producing detectable levels of GST-specific cytokines (TNFα, IL-6, IL-8, IFNγ, IL-12p70, IL-13 and IL-23p19) and also a shift in the GST-specific cytokine response towards a more pro-inflammatory phenotype than that observed before treatment. Participant age and pre-treatment infection status significantly influenced post-treatment cytokine profiles. CONCLUSIONS/SIGNIFICANCE: In areas where schistosomiasis is endemic host age, schistosome infection status and PZQ treatment affect the cellular cytokine response to GST. Thus the efficacy of a GST-based vaccine may also be shaped by the demographic and epidemiological characteristics of targeted populations

The MassiveBlack-II simulation: the evolution of haloes and galaxies to z 0

(Abridged for arXiv)We investigate the properties of halos, galaxies and blackholes to z=0 in the high resolution hydrodynamical simulation MassiveBlack-II (MBII) which evolves a LCDM cosmology in a comoving volume Vbox=100(Mpc/h)^3. MBII is the highest resolution simulation of this size which includes a self-consistent model for star formation, black hole accretion and associated feedback. We provide a simulation browser web application which enables interactive search and tagging of halos, subhalos and their properties and publicly release our galaxy catalogs. Our analysis of the halo mass function (MF) in MBII reveals that baryons have strong effects, with changes in the halo abundance of 20-35% below the knee of the MF (Mhalo < 10^13.2 Msun/h at z=0) when compared to fits based on dark matter only simulations. We provide a fitting function for the halo MF out to redshift z=11 and discuss how the onset of non-universality in the MF limits the accuracy of our fit. We study the halo occupation distribution and clustering of galaxies, in particular the evolution and scale dependence of stochasticity and bias finding reasonable agreement with observational data. The shape of the cosmic spectral energy distribution predicted by MBII is consistent with observations, but lower in amplitude. The Galaxy Stellar Mass Function (GSMF) function is broadly consistent with observations at z>=2. At z<2, the population of passive low mass (for M*<10^9 Msun) galaxies in MBII makes the GSMF too steep compared to observations whereas at the high mass end (M*>10^11 Msun) galaxies hosting bright AGNs make significant contributions to the GSMF. The quasar bolometric luminosity function is also largely consistent with observations. We note however that more efficient AGN feedback (beyond simple thermal coupling used here) is likely necessary for the largest, rarest objects/clusters at low redshifts.Comment: 26 pages, 25 figures. Submitted to MNRAS. High-resolution version and MBII galaxy catalogs can be found at http://mbii.phys.cmu.edu/data