Integration of Mirror Design with Suspension System using NASA's New Mirror Modeling Software

Advances in mirror fabrication is making very large space based telescopes possible. In the many applications, only monolithic mirrors meet the performance requirements. The existing and near-term planned heavy launch vehicles place a premium on lowest possible mass. Again, available and planned payload shroud size limits near term designs to 4 meter class mirror. Practical 8 meter and beyond designs could encourage planners to include larger shrouds if it can be proven that such mirrors can be manufactured. These two factors lower mass and larger mirrors, presents the classic optimization problem. There is a practical upper limit to how large a mirror can be supported by a purely kinematic mount system and be launched. This paper shows how the design of the suspension system and mirror blank needs to be designed simultaneously. We will also explore the concepts of auxiliary support systems, which act only during launch and disengage on orbit. We will define required characteristics of these systems and show how they can substantially reduce the mirror mass. The AMTD project is developing and maturing the processes for future replacements for HUBBLE, creating the design tools, validating the methods and techniques necessary to manufacture, test and launch extremely large optical missions. This paper will use the AMTD 4 meter "design point" as an illustration of the typical use of the modeler in generating the multiple models of mirror and suspension systems used during the conceptual design phase of most projects. The influence of Hexapod geometry, mirror depth, cell size and construction techniques (Exelsis Deep Core Low Temperature Fusion (c) versus Corning Frit Bonded (c) versus Schott Pocket Milled Zerodur (c) in this particular study) are being evaluated. Due to space and time consideration we will only be able to present snippets of the study in this paper. The advances in manufacturing techniques for lightweight mirrors, such as EXELSIS deep core low temperature fusion, Corning's continued improvements in the Frit bonding process and the ability to cast large complex designs, combined with water-jet and conventional diamond

Integration of Mirror Design with Suspension System Using NASA's New Mirror Modeling Software

Advances in mirror fabrication are making very large space based telescopes possible. In many applications, only monolithic mirrors can meet the performance requirements. The existing and near-term planned heavy launch vehicles place a premium on lowest possible mass, and then available payload shroud sizes limit near term designs to 4 meter class mirrors. Practical 8 meter class and beyond designs could encourage planners to include larger shrouds, if it can be proven that such mirrors can be manufactured. These two factors, lower mass and larger mirrors, present the classic optimization problem. There is a practical upper limit to how large of a mirror can be supported by a purely kinematic mount system handling both operational and launch loads. This paper shows how the suspension system and mirror blank need to be designed simultaneously. We will also explore the concepts of auxiliary support systems which act only during launch and disengage on orbit. We will define required characteristics of these systems and show how they can substantially reduce the mirror mass

Minimal breast milk transfer of rituximab, a monoclonal antibody used in neurological conditions.

ObjectiveTo determine the transfer of rituximab, an anti-CD20 monoclonal antibody widely used for neurologic conditions, into mature breast milk.MethodsBreast milk samples were collected from 9 women with MS who received rituximab 500 or 1,000 mg intravenous once or twice while breastfeeding from November 2017 to April 2019. Serial breast milk samples were collected before infusion and at 8 hours, 24 hours, 7 days, and 18-21 days after rituximab infusion in 4 patients. Five additional patients provided 1-2 samples at various times after rituximab infusion.ResultsThe median average rituximab concentration in mature breast milk was low at 0.063 μg/mL (range 0.046-0.097) in the 4 patients with serial breast milk collection, with an estimated median absolute infant dose of 0.0094 mg/kg/d and a relative infant dose (RID) of 0.08% (range 0.06%-0.10%). Most patients had a maximum concentration at 1-7 days after infusion. The maximum concentration occurred in a woman with a single breast milk sample and was 0.29 μg/mL at 11 days postinfusion, which corresponds with an estimated RID of 0.33%. Rituximab concentration in milk was virtually undetectable by 90 days postinfusion.ConclusionsWe determined minimal transfer of rituximab into mature breast milk. The RID for rituximab was less than 0.4% and well below theoretically acceptable levels of less than 10%. Low oral bioavailability would probably also limit the absorption of rituximab by the newborn. In women with serious autoimmune neurologic conditions, monoclonal antibody therapy may afford an acceptable benefit to risk ratio, supporting both maternal treatment and breastfeeding

Targeting terminal pathway reduces brain complement activation, amyloid load and synapse loss, and improves cognition in a mouse model of dementia

Complement is dysregulated in the brain in Alzheimer’s Disease and in mouse models of Alzheimer’s disease. Each of the complement derived effectors, opsonins, anaphylatoxins and membrane attack complex (MAC), have been implicated as drivers of disease but their relative contributions remain unclarified. Here we have focussed on the MAC, a lytic and pro-inflammatory effector, in the AppNL−G−F mouse amyloidopathy model. To test the role of MAC, we back-crossed to generate AppNL−G−F mice deficient in C7, an essential MAC component. C7 deficiency ablated MAC formation, reduced synapse loss and amyloid load and improved cognition compared to complement-sufficient AppNL−G−F mice at 8–10 months age. Adding back C7 caused increased MAC formation in brain and an acute loss of synapses in C7-deficient AppNL−G−F mice. To explore whether C7 was a viable therapeutic target, a C7-blocking monoclonal antibody was administered systemically for one month in AppNL−G−F mice aged 8–9 months. Treatment reduced brain MAC and amyloid deposition, increased synapse density and improved cognitive performance compared to isotype control-treated AppNL−G−F mice. The findings implicate MAC as a driver of pathology and highlight the potential for complement inhibition at the level of MAC as a therapy in Alzheimer’s disease

Integration of Mirror Design with Suspension System Using NASA's New Mirror Modeling Software

No abstract availabl

Integration of Mirror Design with Suspension System using NASA's New Mirror Modeling Software

Advances in mirror fabrication are making very large space based telescopes possible. In many applications, only monolithic mirrors can meet the performance requirements. The existing and near-term planned heavy launch vehicles place a premium on lowest possible mass, and then available payload shroud sizes limit near term designs to 4 meter class mirrors. Practical 8 meter class and beyond designs could encourage planners to include larger shrouds, if it can be proven that such mirrors can be manufactured. These two factors, lower mass and larger mirrors, present the classic optimization problem. There is a practical upper limit to how large of a mirror can be supported by a purely kinematic mount system handling both operational and launch loads. This paper shows how the suspension system and mirror blank need to be designed simultaneously. We will also explore the concepts of auxiliary support systems which act only during launch and disengage on orbit. We will define required characteristics of these systems and show how they can substantially reduce the mirror mass

Engineering Specifications derived from Science Requirements

Advanced Mirror Technology Development (AMTD) is a multi-year effort to systematically mature to TRL-6 the critical technologies needed to produce 4-m or larger flight-qualified UVOIR mirrors by 2018 so that a viable mission can be considered by the 2020 Decadal Review. This technology must enable missions capable of both general astrophysics & ultra-high contrast observations of exoplanets. To accomplish our objective, we use a science-driven systems engineering approach. We mature technologies required to enable the highest priority science AND result in a high-performance low-cost low-risk system

Engineering Specification for Large-aperture UVO Space Telescopes Derived from Science Requirements

An advanced large aperture UV/optical UVO space telescope is required for the next generation of astrophysics and exoplanet science. The science requirements of proposed exoplanet and astrophysics missions were used to determine the encircled energy, point spread function stability and thermal environment requirements. These requirements then determine the optical wavefront specification for potential telescope assemblies which can fit inside current and planned launch vehicles. The optical wavefront specification becomes the top level of the error budget that is split into various sources that control the structural, thermal and optical design

Cryogenic Optical Performance of a Lightweighted Mirror Assembly for Future Space Astronomical Telescopes: Correlating Optical Test Results and Thermal Optical Model

A 43cm diameter stacked core mirror demonstrator was interferometrically tested at room temperature down to 250 degrees Kelvin for thermal deformation. The 2.5m radius of curvature spherical mirror assembly was constructed by low temperature fusing three abrasive waterjet core sections between two CNC pocket milled face sheets. The 93% lightweighted Corning ULE mirror assembly represents the current state of the art for future UV, optical, near IR space telescopes. During the multiple thermal test cycles, test results of interferometric test, thermal IR images of the front face were recorded in order to validate thermal optical model

Terminal complement pathway activation drives synaptic Loss in Alzheimer’s disease models

Complement is involved in developmental synaptic pruning and pathological synapse loss in Alzheimer’s disease. It is posited that C1 binding initiates complement activation on synapses; C3 fragments then tag them for microglial phagocytosis. However, the precise mechanisms of complement-mediated synaptic loss remain unclear, and the role of the lytic membrane attack complex (MAC) is unexplored. We here address several knowledge gaps: (i) is complement activated through to MAC at the synapse? (ii) does MAC contribute to synaptic loss? (iii) can MAC inhibition prevent synaptic loss? Novel methods were developed and optimised to quantify C1q, C3 fragments and MAC in total and regional brain homogenates and synaptoneurosomes from WT and AppNL−G−F Alzheimer’s disease model mouse brains at 3, 6, 9 and 12 months of age. The impact on synapse loss of systemic treatment with a MAC blocking antibody and gene knockout of a MAC component was assessed in Alzheimer’s disease model mice. A significant increase in C1q, C3 fragments and MAC was observed in AppNL−G−F mice compared to controls, increasing with age and severity. Administration of anti-C7 antibody to AppNL−G−F mice modulated synapse loss, reflected by the density of dendritic spines in the vicinity of plaques. Constitutive knockout of C6 significantly reduced synapse loss in 3xTg-AD mice. We demonstrate that complement dysregulation occurs in Alzheimer’s disease mice involving the activation (C1q; C3b/iC3b) and terminal (MAC) pathways in brain areas associated with pathology. Inhibition or ablation of MAC formation reduced synapse loss in two Alzheimer’s disease mouse models, demonstrating that MAC formation is a driver of synapse loss. We suggest that MAC directly damages synapses, analogous to neuromuscular junction destruction in myasthenia gravis