Focus determination for the James Webb Space Telescope Science Instruments: A Survey of Methods

The James Webb Space Telescope (JWST) is a segmented deployable telescope that will require on-orbit alignment using the Near Infrared Camera as a wavefront sensor. The telescope will be aligned by adjusting seven degrees of freedom on each of 18 primary mirror segments and five degrees of freedom on the secondary mirror to optimize the performance of the telescope and camera at a wavelength of 2 microns. With the completion of these adjustments, the telescope focus is set and the optical performance of each of the other science instruments should then be optimal without making further telescope focus adjustments for each individual instrument. This alignment approach requires confocality of the instruments after integration and alignment to the composite metering structure, which will be verified during instrument level testing at Goddard Space Flight Center with a telescope optical simulator. In this paper, we present the results from a study of several analytical approaches to determine the focus for each instrument. The goal of the study is to compare the accuracies obtained for each method, and to select the most feasible for use during optical testing

Optical Alignment of the JWST ISIM to the OTE Simulator (OSIM): Current Concept and Design Studies

The James Webb Space Telescope's (JWST) Integrated Science Instrument Module (ISIM) contains the observatory's four science instruments and their support subsystems. During alignment and test of the integrated ISIM at NASA's Goddard Space Flight Center (GSFC), the Optical'telescope element SIMulator (OSIM) will be used to optically stimulate the science instruments to verify their operation and performance. In this paper we present the design of two cryogenic alignment fixtures that will be used to determine and verify the proper alignment of OSIM to ISIM during testing at GSFC. These fixtures, the Master Alignment Target Fixture (MAW) and the ISIM Alignment Target Fixture (IATF), will provide continuous, six degree of freedom feedback to OSIM during initial ambient alignment as well as during cryogenic vacuum testing. These fixtures will allow us to position the OSIM and maintain OSIM-ISIM alignment to better than 10 microns in translation and 250 micro-radians in rotation. We will provide a brief overview of the OSIM system and calibration and we will also discuss the relevance of these fixtures in the context of the overall ISIM alignment and verification plan

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

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6-11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders 1 . They are heritable 2,3 and etiologically related 4,5 behaviors that have been resistant to gene discovery efforts 6–11 . In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures

Identification and selective expansion of functionally superior T cells expressing chimeric antigen receptors

Background: T cells expressing chimeric antigen receptors (CARs) have shown exciting promise in cancer therapy, particularly in the treatment of B-cell malignancies. However, optimization of CAR-T cell production remains a trial-and-error exercise due to a lack of phenotypic benchmarks that are clearly predictive of anti-tumor functionality. A close examination of the dynamic changes experienced by CAR-T cells upon stimulation can improve understanding of CAR–T-cell biology and identify potential points for optimization in the production of highly functional T cells. Methods: Primary human T cells expressing a second-generation, anti-CD19 CAR were systematically examined for changes in phenotypic and functional responses to antigen exposure over time. Multi-color flow cytometry was performed to quantify dynamic changes in CAR-T cell viability, proliferation, as well as expression of various activation and exhaustion markers in response to varied antigen stimulation conditions. Results: Stimulated CAR-T cells consistently bifurcate into two distinct subpopulations, only one of which (CARhi/CD25+) exhibit anti-tumor functions. The use of central memory T cells as the starting population and the resilience—but not antigen density—of antigen-presenting cells used to expand CAR-T cells were identified as critical parameters that augment the production of functionally superior T cells. We further demonstrate that the CARhi/CD25+ subpopulation upregulates PD-1 but is resistant to PD-L1-induced dysfunction. Conclusions: CAR-T cells expanded ex vivo for adoptive T-cell therapy undergo dynamic phenotypic changes during the expansion process and result in two distinct populations with dramatically different functional capacities. Significant and sustained CD25 and CAR expression upregulation is predictive of robust anti-tumor functionality in antigen-stimulated T cells, despite their correlation with persistent PD-1 upregulation. The functionally superior subpopulation can be selectively augmented by careful calibration of antigen stimulation and the enrichment of central memory T-cell type. Electronic supplementary material The online version of this article (doi:10.1186/s12967-015-0519-8) contains supplementary material, which is available to authorized users

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Optical Alignment of the JWST ISIM to the OTE Simulator (OSIM): Current Concept and Design Studies

The James Webb Space Telescope's (JWST) Integrated Science Instrument Module (ISIM) is the scientific payload of the observatory and contai ns four science instruments. During alignment and test of the integrated ISIM (i.e. ISIM + science instruments) at NASA's Goddard Space Fli ght Center (GSFC), the Optical telescope element SIMulator (OSIM) wil l be used to optically stimulate the science instruments to verify their operation and performance. In this paper we present the design of two cryogenic alignment fixtures that will be used to determine and verify the proper alignment of OSIM to ISIM during testing at GSFC. The se fixtures, the Master Alignment Target Fixture (MATF) and the ISIM Alignment Target Fixture (IATF), will provide continuous, 6 degree of freedom feedback to OSIM during initial ambient alignment as well as during cryogenic vacuum testing