Prox-1: Automated Proximity Operations on an ESPA Class Platform

The Georgia Institute of Technology Prox-1 mission is an ESPA-class, student-designed, student-built satellite mission designed to demonstrate automated relative trajectory control in conjunction with a semi-cooperative target in Low-Earth Orbit. It is scheduled for launch in September of 2016 aboard the Department of Defense Space Test Program (STP-2) mission as a secondary payload. The primary mission of the spacecraft is to perform flight qualification and performance validation of experimental flight hardware; to deploy The Planetary Society’s LightSail mission, an internally housed 3U cubesat; and to perform relative trajectory control with respect to that target utilizing passive thermal imaging and automated on-board guidance algorithms. Several subsystems are integrated to accomplish this mission, and a description of the subsystem components is detailed in this paper. An overview of the concept operations is also presented here. For the automated proximity operations phase of the mission, Prox-1 will demonstrate an advanced Guidance, Navigation, & Control subsystem. This subsystem will combine GN&C algorithms and filters developed in-house and based on reference literature. This paper will provide an overview of the Prox-1 mission and the advancements it brings to the small satellite community

Efficiency, selectivity and robustness of the nuclear pore complex transport

All materials enter or exit the cell nucleus through nuclear pore complexes (NPCs), efficient transport devices that combine high selectivity and throughput. A central feature of this transport is the binding of cargo-carrying soluble transport factors to flexible, unstructured proteinaceous filaments called FG-nups that line the NPC. We have modeled the dynamics of transport factors and their interaction with the flexible FG-nups as diffusion in an effective potential, using both analytical theory and computer simulations. We show that specific binding of transport factors to the FG-nups facilitates transport and provides the mechanism of selectivity. We show that the high selectivity of transport can be accounted for by competition for both binding sites and space inside the NPC, which selects for transport factors over other macromolecules that interact only non-specifically with the NPC. We also show that transport is relatively insensitive to changes in the number and distribution of FG-nups in the NPC, due mainly to their flexibility; this accounts for recent experiments where up to half of the total mass of the NPC has been deleted, without abolishing the transport. Notably, we demonstrate that previously established physical and structural properties of the NPC can account for observed features of nucleocytoplasmic transport. Finally, our results suggest strategies for creation of artificial nano-molecular sorting devices.Comment: 38 pages, six figure

The Transient Dendritic Solidification Experiment (TDSE)

The study of steady-state dendritic growth has both validated many element of transport phenomena in dendritic growth, and yielded many new insights. Further development in simulation and modeling are needed, as is further understanding of the role of selection or scaling in dendritic growth. The TDSE contributes to the further study of dendritic phenomena by carefully measuring and modeling transient effects on dendritic growth. The major challenge encountered in measuring and analyzing the transient behavior of isothermal dendrites is defining precisely the initial conditions from which or to which the dendrite evolves. Our proposed pressure-mediated TDSE microgravity experiment, obviates this difficulty, because the transient occurs between two well-characterized steady-states, rather than between an ill-defined initial state and the final steady state. The major results expected are unique data on transient behavior that will extend the scientific bounds from the now well-understood thermal effects, and provide insight into interfacial dynamics where open questions remain

Nonprofit governance: Improving performance in troubled economic times

Nonprofit management is currently pressured to perform effectively in a weak economy. Yet, nonprofit governance continues to suffer from unclear conceptions of the division of labor between board of directors and executive directors. This online survey of 114 executive directors aims to provide clarification and recommendations for social administration

Hypertriglyceridemia and Recurrent Pancreatitis following Splenectomy

Hyperlipoproteinemia represents a constellation of clinical syndromes that frequently includes hypertriglyceridemia. Because of the degree of elevation in the triglyceride levels frequently seen in these syndromes, they are associated with complications not generally observed among those patients with essential hypertriglyceridemia, including as in this case report, recurrent pancreatitis. Here, we present a case of a patient with hyperlipoproteinemia who developed acute worsening of his hypertriglyceridemia and onset of acute panceatitis that became recurrent following elective splenectomy for suspected lymphoma. In particular, we discuss the dietary management of hypertriglyceridemia which significantly reduced the number of episodes of acute pancreatitis in this patient

Discovery and characterisation of a novel toxin from Dendroaspis angusticeps, named Tx7335, that activates the potassium channel KcsA

Due to their central role in essential physiological processes, potassium channels are common targets for animal toxins. These toxins in turn are of great value as tools for studying channel function and as lead compounds for drug development. Here, we used a direct toxin pull-down assay with immobilised KcsA potassium channel to isolate a novel KcsA-binding toxin (called Tx7335) from eastern green mamba snake (Dendroaspis angusticeps) venom. Sequencing of the toxin by Edman degradation and mass spectrometry revealed a 63 amino acid residue peptide with 4 disulphide bonds that belongs to the three-finger toxin family, but with a unique modification of its disulphide-bridge scaffold. The toxin induces a dose-dependent increase in both open probabilities and mean open times on KcsA in artificial bilayers. Thus, it unexpectedly behaves as a channel activator rather than an inhibitor. A charybdotoxinsensitive mutant of KcsA exhibits similar susceptibility to Tx7335 as wild-type, indicating that the binding site for Tx7335 is distinct from that of canonical pore-blocker toxins. Based on the extracellular location of the toxin binding site (far away from the intracellular pH gate), we propose that Tx7335 increases potassium flow through KcsA by allosterically reducing inactivation of the channel

Preferential Phosphorylation of R-domain Serine 768 Dampens Activation of CFTR Channels by PKA

CFTR (cystic fibrosis transmembrane conductance regulator), the protein whose dysfunction causes cystic fibrosis, is a chloride ion channel whose gating is controlled by interactions of MgATP with CFTR's two cytoplasmic nucleotide binding domains, but only after several serines in CFTR's regulatory (R) domain have been phosphorylated by cAMP-dependent protein kinase (PKA). Whereas eight R-domain serines have previously been shown to be phosphorylated in purified CFTR, it is not known how individual phosphoserines regulate channel gating, although two of them, at positions 737 and 768, have been suggested to be inhibitory. Here we show, using mass spectrometric analysis, that Ser 768 is the first site phosphorylated in purified R-domain protein, and that it and five other R-domain sites are already phosphorylated in resting Xenopus oocytes expressing wild-type (WT) human epithelial CFTR. The WT channels have lower activity than S768A channels (with Ser 768 mutated to Ala) in resting oocytes, confirming the inhibitory influence of phosphoserine 768. In excised patches exposed to a range of PKA concentrations, the open probability (Po) of mutant S768A channels exceeded that of WT CFTR channels at all [PKA], and the half-maximally activating [PKA] for WT channels was twice that for S768A channels. As the open burst duration of S768A CFTR channels was almost double that of WT channels, at both low (55 nM) and high (550 nM) [PKA], we conclude that the principal mechanism by which phosphoserine 768 inhibits WT CFTR is by hastening the termination of open channel bursts. The right-shifted Po-[PKA] curve of WT channels might explain their slower activation, compared with S768A channels, at low [PKA]. The finding that phosphorylation kinetics of WT or S768A R-domain peptides were similar provides no support for an alternative explanation, that early phosphorylation of Ser 768 in WT CFTR might also impair subsequent phosphorylation of stimulatory R-domain serines. The observed reduced sensitivity to activation by [PKA] imparted by Ser 768 might serve to ensure activation of WT CFTR by strong stimuli while dampening responses to weak signals

Protection of nascent DNA at stalled replication forks is mediated by phosphorylation of RIF1 intrinsically disordered region

Acknowledgements We thank all members of the Di Virgilio lab for their feedback and discussion; V Delgado-Benito (Di Virgilio lab, MDC, Berlin) for her contribution to the project development; L Keller (Di Virgilio lab, MDC, Berlin) for support with cloning, mutagenesis, and mice genotyping; C Brischetto (Scheidereit Lab, MDC, Berlin) for assistance with confocal microscopy; Aberdeen Proteomics facility (University of Aberdeen) for the mass spec analysis of Aph-induced hRIF1 phosphorylation; and the MDC FACS Core Facility and Dr. HP Rahn for support with cell sorting. Aliquots of ATRi and ATMi were gener- ously provided by AG Henssen (MDC and ECRC, Berlin). Figures 1B and D, 2A, and 4C contain items created with BioRender.com. This work was supported by ERC grant 638897 (to MDV), the Helmholtz- Gemeinschaft Zukunftsthema 'Immunology and Inflammation' ZT-0027 (to MDV), P41 GM109824 and P41 GM103314 (to BTC), and Cancer Research UK awards C1445/A19059 and DRCPGM\100,013 (to ADD and SH).Peer reviewedPublisher PD