Creating the Future of Microspace Technology

The Advanced Space Technology Program (ASTP) at the Defense Advanced Research Projects Agency (DARPA) has recently initiated a series of technology development efforts as part of its drive to enhance the cost effectiveness and responsiveness of defense space systems. These efforts focus on reducing spacecraft size, cost, weight, and power consumption, while simultaneously improving performance. The technology initiatives which are underway span a broad spectrum of efforts at the satellite system and subsystem levels, as well as some which focus on individual components and materials. The technology initiatives which DARPA is pursuing will enhance large, major satellites via technology insertions of cost effective, leading edge technologies in a timely fashion, and will facilitate a new class of small highly capable satellites. This paper will highlight some of the new efforts which have been initiated by ASTP in the past year

Production of large-particle-size monodisperse latexes

The research program achieved two objectives: (1) it has refined and extended the experimental techniques for preparing monodisperse latexes in quantity on the ground up to a particle diameter of 10 microns; and (2) it has demonstrated that a microgravity environment can be used to grow monodisperse latexes to larger sizes, where the limitations in size have yet to be defined. The experimental development of the monodisperse latex reactor (MLR) and the seeded emulsion polymerizations carried out in the laboratory prototype of the flight hardware, as a function of the operational parameters is discussed. The emphasis is directed towards the measurement, interpretation, and modeling of the kinetics of seeded emulsion polymerization and successive seeded emulsion polymerization. The recipe development of seeded emulsion polymerization as a function of particle size is discussed. The equilibrium swelling of latex particles with monomers was investigated both theoretically and experimentally. Extensive studies are reported on both the type and concentration of initiators, surfactants, and inhibitors, which eventually led to the development of the flight recipes. The experimental results of the flight experiments are discussed, as well as the experimental development of inhibition of seeded emulsion polymerization in terms of time of inhibition and the effect of inhibitors on the kinetics of polymerization

The first products made in space: Monodisperse latex particles

The preparation of large particle size 3 to 30 micrometer monodisperse latexes in space confirmed that original rationale unequivocally. The flight polymerizations formed negligible amounts of coagulum as compared to increasing amounts for the ground-based polymerizations. The number of offsize large particles in the flight latexes was smaller than in the ground-based latexes. The particle size distribution broadened and more larger offsize particles were formed when the polymerizations of the partially converted STS-4 latexes were completed on Earth. Polymerization in space also showed other unanticipated advantages. The flight latexes had narrower particle size distributions than the ground-based latexes. The particles of the flight latexes were more perfect spheres than those of the ground-based latexes. The superior uniformity of the flight latexes was confirmed by the National Bureau of Standards acceptance of the 10 micrometer STS-6 latex and the 30 micrometer STS-11 latexes as Standard Reference Materials, the first products made in space for sale on Earth. The polymerization rates in space were the same as those on Earth within experimental error. Further development of the ground-based polymerization recipes gave monodisperse particles as large as 100 micrometer with tolerable levels of coagulum, but their uniformity was significantly poorer than the flight latexes. Careful control of the polymerization parameters gave uniform nonspherical particles: symmetrical and asymmetrical doublets, ellipsoids, egg-shaped, ice cream cone-shaped, and popcorn-shaped particles

Changes in the folding landscape of the WW domain provide a molecular mechanism for an inherited genetic syndrome

WW domains are small domains present in many human proteins with a wide array of functions and acting through the recognition of proline-rich sequences. The WW domain belonging to polyglutamine tract-binding protein 1 (PQBP1) is of particular interest due to its direct involvement in several X chromosome-linked intellectual disabilities, including Golabi-Ito-Hall (GIH) syndrome, where a single point mutation (Y65C) correlates with the development of the disease. The mutant cannot bind to its natural ligand WBP11, which regulates mRNA processing. In this work we use high-field high-resolution NMR and enhanced sampling molecular dynamics simulations to gain insight into the molecular causes the disease. We find that the wild type protein is partially unfolded exchanging among multiple beta-strand-like conformations in solution. The Y65C mutation further destabilizes the residual fold and primes the protein for the formation of a disulphide bridge, which could be at the origin of the loss of function

WW Domains of the Yes-Kinase-Associated-Protein (YAP) Transcriptional Regulator Behave as Independent Units with Different Binding Preferences for PPxY Motif-Containing Ligands

YAP is a WW domain-containing effector of the Hippo tumor suppressor pathway, and the object of heightened interest as a potent oncogene and stemness factor. YAP has two major isoforms that differ in the number of WW domains they harbor. Elucidating the degree of co-operation between these WW domains is important for a full understanding of the molecular function of YAP. We present here a detailed biophysical study of the structural stability and binding properties of the two YAP WW domains aimed at investigating the relationship between both domains in terms of structural stability and partner recognition. We have carried out a calorimetric study of the structural stability of the two YAP WW domains, both isolated and in a tandem configuration, and their interaction with a set of functionally relevant ligands derived from PTCH1 and LATS kinases. We find that the two YAP WW domains behave as independent units with different binding preferences, suggesting that the presence of the second WW domain might contribute to modulate target recognition between the two YAP isoforms. Analysis of structural models and phage-display studies indicate that electrostatic interactions play a critical role in binding specificity. Together, these results are relevant to understand of YAP function and open the door to the design of highly specific ligands of interest to delineate the functional role of each WW domain in YAP signaling.This work was supported by the Spanish Ministry of Education and Science [grant BIO2009-13261-CO2], the Spanish Ministry of Economy and Competitivity [grant BIO2012-39922-CO2] including FEDER (European Funds for Regional Development) funds and the Governement of Andalusia [grant CVI-5915]. Marius Sudol was supported by PA Breast Cancer Coalition Grants (#60707 and #920093) plus the Geisinger Clinic