98 research outputs found
JWST mirror and actuator performance at cryo-vacuum
The James Webb Space Telescope (JWST) telescope’s Secondary Mirror Assembly (SMA) and eighteen Primary Mirror Segment Assemblies (PMSAs) are each actively controlled in rigid body position via six hexapod actuators. Each of the PMSAs additionally has a radius of curvature actuator. The mirrors are stowed to the mirror support structure to survive the launch environment and then must be deployed 12.5 mm to reach the nominally deployed position before the Wavefront Sensing & Control (WFSC) alignment and phasing process begins. JWST requires testing of the full optical system in a Cryogenic Vacuum (CV) environment before launch. The cryo vacuum test campaign was executed in Chamber A at the Johnson Space Center (JSC) in Houston Texas. The test campaign consisted of an ambient vacuum test, a cooldown test, a cryo stable test at 65 Kelvin, a warmup test, and finally a second ambient vacuum test. Part of that test campaign was the functional and performance testing of the hexapod actuators on the flight mirrors. This paper will describe the testing that was performed on all 132 hexapod and radius of curvature actuators. The test campaign first tests actuators individually then tested how the actuators perform in the hexapod system. Telemetry from flight sensors on the actuators and measurements from external metrology devices such as interferometers, photogrammetry systems and image analysis was used to demonstrate the performance of the JWST actuators. The mirror move commanding process was exercised extensively during the JSC CV test and many examples of accurately commanded moves occurred. The PMSA and SMA actuators performed extremely well during the JSC CV test, and we have demonstrated that the actuators are fully functional both at ambient and cryo temperatures and that the mirrors will go to their commanded positions with the accuracy needed to phase and align the telescope
Discrete molecular dynamics can predict helical prestructured motifs in disordered proteins.
Intrinsically disordered proteins (IDPs) lack a stable tertiary structure, but their short binding regions termed Pre-Structured Motifs (PreSMo) can form transient secondary structure elements in solution. Although disordered proteins are crucial in many biological processes and designing strategies to modulate their function is highly important, both experimental and computational tools to describe their conformational ensembles and the initial steps of folding are sparse. Here we report that discrete molecular dynamics (DMD) simulations combined with replica exchange (RX) method efficiently samples the conformational space and detects regions populating alpha-helical conformational states in disordered protein regions. While the available computational methods predict secondary structural propensities in IDPs based on the observation of protein-protein interactions, our ab initio method rests on physical principles of protein folding and dynamics. We show that RX-DMD predicts alpha-PreSMos with high confidence confirmed by comparison to experimental NMR data. Moreover, the method also can dissect alpha-PreSMos in close vicinity to each other and indicate helix stability. Importantly, simulations with disordered regions forming helices in X-ray structures of complexes indicate that a preformed helix is frequently the binding element itself, while in other cases it may have a role in initiating the binding process. Our results indicate that RX-DMD provides a breakthrough in the structural and dynamical characterization of disordered proteins by generating the structural ensembles of IDPs even when experimental data are not available
JWST mirror and actuator performance at cryo-vacuum
The James Webb Space Telescope (JWST) telescope’s Secondary Mirror Assembly (SMA) and eighteen Primary Mirror Segment Assemblies (PMSAs) are each actively controlled in rigid body position via six hexapod actuators. Each of the PMSAs additionally has a radius of curvature actuator. The mirrors are stowed to the mirror support structure to survive the launch environment and then must be deployed 12.5 mm to reach the nominally deployed position before the Wavefront Sensing & Control (WFSC) alignment and phasing process begins. JWST requires testing of the full optical system in a Cryogenic Vacuum (CV) environment before launch. The cryo vacuum test campaign was executed in Chamber A at the Johnson Space Center (JSC) in Houston Texas. The test campaign consisted of an ambient vacuum test, a cooldown test, a cryo stable test at 65 Kelvin, a warmup test, and finally a second ambient vacuum test. Part of that test campaign was the functional and performance testing of the hexapod actuators on the flight mirrors. This paper will describe the testing that was performed on all 132 hexapod and radius of curvature actuators. The test campaign first tests actuators individually then tested how the actuators perform in the hexapod system. Telemetry from flight sensors on the actuators and measurements from external metrology devices such as interferometers, photogrammetry systems and image analysis was used to demonstrate the performance of the JWST actuators. The mirror move commanding process was exercised extensively during the JSC CV test and many examples of accurately commanded moves occurred. The PMSA and SMA actuators performed extremely well during the JSC CV test, and we have demonstrated that the actuators are fully functional both at ambient and cryo temperatures and that the mirrors will go to their commanded positions with the accuracy needed to phase and align the telescope
Unifying view of mechanical and functional hotspots across class A GPCRs
G protein-coupled receptors (GPCRs) are the largest superfamily of signaling proteins. Their activation process is accompanied by conformational changes that have not yet been fully uncovered. Here, we carry out a novel comparative analysis of internal structural fluctuations across a variety of receptors from class A GPCRs, which currently has the richest structural coverage. We infer the local mechanical couplings underpinning the receptors' functional dynamics and finally identify those amino acids whose virtual deletion causes a significant softening of the mechanical network. The relevance of these amino acids is demonstrated by their overlap with those known to be crucial for GPCR function, based on static structural criteria. The differences with the latter set allow us to identify those sites whose functional role is more clearly detected by considering dynamical and mechanical properties. Of these sites with a genuine mechanical/dynamical character, the top ranking is amino acid 7x52, a previously unexplored, and experimentally verifiable key site for GPCR conformational response to ligand binding. \ua9 2017 Ponzoni et al
The James Webb Space Telescope Mission: Optical Telescope Element Design, Development, and Performance
The James Webb Space Telescope (JWST) is a large, infrared space telescope
that has recently started its science program which will enable breakthroughs
in astrophysics and planetary science. Notably, JWST will provide the very
first observations of the earliest luminous objects in the Universe and start a
new era of exoplanet atmospheric characterization. This transformative science
is enabled by a 6.6 m telescope that is passively cooled with a 5-layer
sunshield. The primary mirror is comprised of 18 controllable, low areal
density hexagonal segments, that were aligned and phased relative to each other
in orbit using innovative image-based wavefront sensing and control algorithms.
This revolutionary telescope took more than two decades to develop with a
widely distributed team across engineering disciplines. We present an overview
of the telescope requirements, architecture, development, superb on-orbit
performance, and lessons learned. JWST successfully demonstrates a segmented
aperture space telescope and establishes a path to building even larger space
telescopes.Comment: accepted by PASP for JWST Overview Special Issue; 34 pages, 25
figure
The James Webb Space Telescope Mission
Twenty-six years ago a small committee report, building on earlier studies,
expounded a compelling and poetic vision for the future of astronomy, calling
for an infrared-optimized space telescope with an aperture of at least .
With the support of their governments in the US, Europe, and Canada, 20,000
people realized that vision as the James Webb Space Telescope. A
generation of astronomers will celebrate their accomplishments for the life of
the mission, potentially as long as 20 years, and beyond. This report and the
scientific discoveries that follow are extended thank-you notes to the 20,000
team members. The telescope is working perfectly, with much better image
quality than expected. In this and accompanying papers, we give a brief
history, describe the observatory, outline its objectives and current observing
program, and discuss the inventions and people who made it possible. We cite
detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space
Telescope Overview, 29 pages, 4 figure
The bear in Eurasian plant names: Motivations and models
Ethnolinguistic studies are important for understanding an ethnic group's ideas on the world, expressed in its language. Comparing corresponding aspects of such knowledge might help clarify problems of origin for certain concepts and words, e.g. whether they form common heritage, have an independent origin, are borrowings, or calques. The current study was conducted on the material in Slavonic, Baltic, Germanic, Romance, Finno-Ugrian, Turkic and Albanian languages. The bear was chosen as being a large, dangerous animal, important in traditional culture, whose name is widely reflected in folk plant names. The phytonyms for comparison were mostly obtained from dictionaries and other publications, and supplemented with data from databases, the co-authors' field data, and archival sources (dialect and folklore materials). More than 1200 phytonym use records (combinations of a local name and a meaning) for 364 plant and fungal taxa were recorded to help find out the reasoning behind bear-nomination in various languages, as well as differences and similarities between the patterns among them. Among the most common taxa with bear-related phytonyms were Arctostaphylos uva-ursi (L.) Spreng., Heracleum sphondylium L., Acanthus mollis L., and Allium ursinum L., with Latin loan translation contributing a high proportion of the phytonyms. Some plants have many and various bear-related phytonyms, while others have only one or two bear names. Features like form and/or surface generated the richest pool of names, while such features as colour seemed to provoke rather few associations with bears. The unevenness of bear phytonyms in the chosen languages was not related to the size of the language nor the present occurence of the Brown Bear in the region. However, this may, at least to certain extent, be related to the amount of the historical ethnolinguistic research done on the selected languages
Paleoclimatic control of biogeographic and sedimentary events in Tethyan and peri-Tethyan areas during the Oxfordian (Late Jurassic)
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
Letter from Raymond F. Koby to Springfield College (June 28, 1918)
A letter from Raymond F. Koby to Springfield College written on June 28, 1918. In the letter, Koby writes how he enclosed $15 towards the class of 2016.Raymond F. Koby graduated from Springfield College in 1916. He went into the service in 1917 to fight in World War I. After the war he would become a Physical Director for the Y.M.C.A. in Superior, Wisconsin for 8 years before becoming the General Secretary to their Y.M.C.A. for 23 years until he retired
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