IL-17 Production from T Helper 17, Mucosal-Associated Invariant T, and γδ Cells in Tuberculosis Infection and Disease.

IL-17-producing cells have been shown to be important in the early stages of Mycobacterium tuberculosis (Mtb) infection in animal models. However, there are very little data on the role of IL-17 in human studies of tuberculosis (TB). We recruited TB patients and their highly exposed contacts who were further categorized based on results from an IFN-γ-release assay (IGRA): (1) IGRA positive (IGRA+) at recruitment (latently TB infected), (2) IGRA negative (IGRA-) at recruitment and 6 months [non-converters (NC)], and (3) IGRA- at recruitment and IGRA+ at 6 months (converters). Whole blood was stimulated with mycobacterial antigens and analyzed using T helper (Th) 17 multiplex cytokine assays. Th17, Vγ9Vδ2+, and CD161++Vα7.2+ mucosal-associated invariant T (MAIT) cells were analyzed by flow cytometry. The majority of IL-17 was produced by CD26+CD4+ Th17 cells (median 71%) followed by γδ T cells (6.4%) and MAIT cells (5.8%). TB patients had a significantly lower proportion of Th17 cells and CD4+CD161+Vα7.2+ cells producing both IL-17 and IFN-γ compared to LTBI subjects. IGRA NC had significantly lower levels of CD26-CD4+ and CD8+ MAIT cells producing IL-17 compared to IGRA C but had significantly higher levels of IL-17A, IL-17F, IL-21, and IL-23 in ESAT-6/CFP-10-stimulated supernatants compared to IGRA C. These data provide new insights into the role of IL-17 and IL-17-producing cells at three key stages of the Mtb infection spectrum

MetaIPM: Placing Integral Projection Models Into a Metapopulation Framework

1. Metapopulation models include spatial population dynamics such as dispersion and migration between subpopulations. Integral projection models (IPMs) can include demographic rates as a function of size. Traditionally, metapopulation models do not included detailed populaiton models such as IPMs. In some situations, both local population dynamics (e.g. size-based survival) and spatial dynamics are important. 2. We present a Python package, MetaIPM, which places IPMs into a metapopulation framework, and allow users to readily construct and apply these models that combine local population dynamics within a metapopulation framework. 3. MetaIPM includes an IPM for each subpopulation that is connected to other subpopulations via a metapopulation movement model. These movements can include dispersion, migration or other patterns. The IPM can include for size-specific demographic rates (e.g. survival, recruitment) as well as management actions, such as length-based harvest (e.g. gear specific capture sizes, varying slot limits across political boundaries). The model also allows for changes in metapopulation connectivity between locations, such as a fish passage ladders to enhance movement or deterrents to reduce movement. Thus, resource managers can use MetaIPM to compare different management actions such as the harvest gear type (which can be length-specific) and harvest locations. 4. We demonstrate how MetaIPM may be applied to inform managers seeking to limit the spread of an invasive species in a system with important metapopulation dynamics. Specifically, we compared removal lengths (all length fish versus longer fish only) for an invasive fish population in a fragmented, inland river system. MetaIPM allowed users to compare the importance of harvesting source populations away from the invasion front, as well as species at the invasion front. The model would also allow for future comparisons of different deterrent placement locations in the system. 5. Moving beyond our example system, we describe how MetaIPM can be applied to other species, systems and management approaches. The MetaIPM packages includes Jupyter Notebooks documenting the package as well as a second set of JupyterNotebooks showing the application of the package to our example system

Standardizing kilonovae and their use as standard candles to measure the Hubble constant

The detection of GW170817 is revolutionizing many areas of astrophysics with the joint observation of gravitational waves and electromagnetic emissions. These multimessenger events provide a new approach to determine the Hubble constant, thus, they are a promising candidate for mitigating the tension between measurements of type-Ia supernovae via the local distance ladder and the cosmic microwave background. In addition to the "standard siren"provided by the gravitational-wave measurement, the kilonova itself has characteristics that allow one to improve existing measurements or to perform yet another, independent measurement of the Hubble constant without gravitational-wave information. Here, we employ standardization techniques borrowed from the type-Ia community and apply them to kilonovae, not using any information from the gravitational-wave signal. We use two versions of this technique, one derived from direct observables measured from the light curve, and the other based on inferred ejecta parameters, e.g., mass, velocity, and composition, for two different models. These lead to Hubble constant measurements of H0=109-35+49 km s-1 Mpc-1 for the measured analysis, and H0=85-17+22 km s-1 Mpc-1 and H0=79-15+23 km s-1 Mpc-1 for the inferred analyses. This measurement has error bars within ∼2 to the gravitational-wave measurements (H0=74-8+16 km s-1 Mpc-1), showing its promise as an independent constraint on H0

Measuring the Hubble constant with a sample of kilonovae

Kilonovae produced by the coalescence of compact binaries with at least one neutron star are promising standard sirens for an independent measurement of the Hubble constant (H0). Through their detection via follow-up of gravitational-wave (GW), short gamma-ray bursts (sGRBs) or optical surveys, a large sample of kilonovae (even without GW data) can be used for H0 contraints. Here, we show measurement of H0 using light curves associated with four sGRBs, assuming these are attributable to kilonovae, combined with GW170817. Including a systematic uncertainty on the models that is as large as the statistical ones, we find H0 ¼ 73:8þ6:3 5:8 km s1 Mpc1 and H0 ¼ 71:2þ3:2 3:1 km s1 Mpc1 for two different kilonova models that are consistent with the local and inverse-distance ladder measurements. For a given model, this measurement is about a factor of 2-3 more precise than the standard-siren measurement for GW170817 using only GWs

Developmental Cryogenic Active Telescope Testbed, a Wavefront Sensing and Control Testbed for the Next Generation Space Telescope

As part of the technology validation strategy of the next generation space telescope (NGST), a system testbed is being developed at GSFC, in partnership with JPL and Marshall Space Flight Center (MSFC), which will include all of the component functions envisioned in an NGST active optical system. The system will include an actively controlled, segmented primary mirror, actively controlled secondary, deformable, and fast steering mirrors, wavefront sensing optics, wavefront control algorithms, a telescope simulator module, and an interferometric wavefront sensor for use in comparing final obtained wavefronts from different tests. The developmental. cryogenic active telescope testbed (DCATT) will be implemented in three phases. Phase 1 will focus on operating the testbed at ambient temperature. During Phase 2, a cryocapable segmented telescope will be developed and cooled to cryogenic temperature to investigate the impact on the ability to correct the wavefront and stabilize the image. In Phase 3, it is planned to incorporate industry developed flight-like components, such as figure controlled mirror segments, cryogenic, low hold power actuators, or different wavefront sensing and control hardware or software. A very important element of the program is the development and subsequent validation of the integrated multidisciplinary models. The Phase 1 testbed objectives, plans, configuration, and design will be discussed

Inborn Errors of Immunity on the Island of Ireland - a Cross-Jurisdictional UKPID/ESID Registry Report

The epidemiology of inborn errors of immunity (IEI) in the Republic of Ireland was first published in 2005 but has not been updated since. IEI prevalence data from Northern Ireland was last published in 2018. Using data from the United Kingdom Primary Immune Deficiency (UKPID) and European Society for Immunodeficiencies (ESID) registries, we reviewed all registered cases of IEI affecting adult patients ≥ 18 years of age from the two largest immunology specialist centres in Northern Ireland and the Republic of Ireland, respectively and calculated the combined minimum adult prevalence of IEI on the island of Ireland for the first time. We also recorded data pertaining to presenting symptoms of IEI, diagnostic delay, immunoglobulin data, and genetic testing, as well as briefly reporting data pertaining to secondary immunodeficiency in both countries. As of 1 May 2020, we identified a minimum adult IEI prevalence in Ireland of 8.85/100,000 population

Inborn Errors of Immunity on the Island of Ireland - a Cross-Jurisdictional UKPID/ESID Registry Report

Correction; Early Access:The epidemiology of inborn errors of immunity (IEI) in the Republic of Ireland was first published in 2005 but has not been updated since. IEI prevalence data from Northern Ireland was last published in 2018. Using data from the United Kingdom Primary Immune Deficiency (UKPID) and European Society for Immunodeficiencies (ESID) registries, we reviewed all registered cases of IEI affecting adult patients >= 18 years of age from the two largest immunology specialist centres in Northern Ireland and the Republic of Ireland, respectively and calculated the combined minimum adult prevalence of IEI on the island of Ireland for the first time. We also recorded data pertaining to presenting symptoms of IEI, diagnostic delay, immunoglobulin data, and genetic testing, as well as briefly reporting data pertaining to secondary immunodeficiency in both countries. As of 1 May 2020, we identified a minimum adult IEI prevalence in Ireland of 8.85/100,000 population.Peer reviewe

Science Hybrid Orbiter and Lunar Relay (SCHOLR) Architecture and Design

Considered both a stepping-stone to deep space and a key to unlocking the mysteries of planetary formation, the Moon offers a unique opportunity for scientific study. Robotic precursor missions are being developed to improve technology and enable new approaches to exploration. Robots, lunar landers, and satellites play significant roles in advancing science and technologies, offering close range and in-situ observations. Science and exploration data gathered from these nodes and a lunar science satellite is intended to support future human expeditions and facilitate future utilization of lunar resources. To attain a global view of lunar science, the nodes will be distributed over the lunar surface, including locations on the far side of the Moon. Given that nodes on the lunar far side do not have direct line-of-sight for Earth communications, the planned presence of such nodes creates the need for a lunar communications relay satellite. Since the communications relay capability would only be required for a small portion of the satellite s orbit, it may be possible to include communication relay components on a science spacecraft. Furthermore, an integrated satellite has the potential to reduce lunar surface mission costs. A SCience Hybrid Orbiter and Lunar Relay (SCHOLR) is proposed to accomplish scientific goals while also supporting the communications needs of landers on the far side of the Moon. User needs and design drivers for the system were derived from the anticipated needs of future robotic and lander missions. Based on these drivers and user requirements, accommodations for communications payload aboard a science spacecraft were developed. A team of interns identified and compared possible SCHOLR architectures. The final SCHOLR architecture was analyzed in terms of orbiter lifetime, lunar surface coverage, size, mass, power, and communications data rates. This paper presents the driving requirements, operational concept, and architecture views for SCHOLR within a lunar surface nodal network. Orbital and bidirectional link analysis, between lunar nodes, orbiter, and Earth, as well as a conceptual design for the spacecraft are also presente

Measurement of CD4+ and CD8+ T-Lymphocyte Cytokine Secretion and Gene Expression Changes in p-Phenylenediamine Allergic Patients and Tolerant Individuals

Factors predisposing to individual susceptibility to contact allergic dermatitis are ill defined. This study was designed to characterize the response of allergic and tolerant individuals’ T-lymphocytes after exposure to p-phenylenediamine (PPD). Peripheral blood mononuclear cells (PBMCs) from allergic patients proliferated when treated with PPD and Bandrowski's base (BB) and secreted IL-1α, -1β, -4, -5, -6, -8, -10, and -13; IFN-γ; tumor necrosis factor-α; MIP-1α/β; MCP-1 (monocyte chemotactic protein-1); and RANTES. PBMCs from tolerant individuals were stimulated to proliferate only with BB, and they secreted significantly lower levels of Th2 cytokines. Principal component analysis showed that genes are differentially expressed between the patient groups. A network-based analysis of microarray data showed upregulation of T helper type 2 (Th2) gene pathways, including IL-9, in allergic patients, but a regulatory gene profile in tolerant individuals. Real-time PCR confirmed the observed increase in Th2 cytokine gene transcription in allergic patients. Purified CD4+ and CD8+ T cells from allergic patients were stimulated to proliferate and secrete Th2 cytokines following antigen exposure. Only CD4+ T cells from tolerant individuals were stimulated by BB, and levels of Th2 cytokines were 80% lower. The nature of the antigenic determinant stimulating PBMCs and levels of Th2 cytokines, including IL-9, was confirmed in a validation cohort. These studies show increased activity of Th2 cytokines in CD4+ and CD8+ T cells from individuals with allergic contact dermatitis