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Structural Studies of Inositol 1,4,5-Trisphosphate Receptor COUPLING LIGAND BINDING TO CHANNEL GATING

The three isoforms of the inositol 1,4,5-trisphosphate receptor (IP{sub 3}R) exhibit distinct IP{sub 3} sensitivities and cooperativities in calcium (Ca{sup 2+}) channel function. The determinants underlying this isoform-specific channel gating mechanism have been localized to the N-terminal suppressor region of IP3R. We determined the 1.9 {angstrom} crystal structure of the suppressor domain from type 3 IP{sub 3}R (IP{sub 3}R3{sub SUP}, amino acids 1-224) and revealed structural features contributing to isoform-specific functionality of IP{sub 3}R by comparing it with our previously determined structure of the type 1 suppressor domain (IP{sub 3}R1{sub SUP}). The molecular surface known to associate with the ligand binding domain (amino acids 224-604) showed marked differences between IP{sub 3}R3{sub SUP} and IP{sub 3}R1{sub SUP}. Our NMR and biochemical studies showed that three spatially clustered residues (Glu-20, Tyr-167, and Ser-217 in IP{sub 3}R1 and Glu-19, Trp-168, and Ser-218 in IP{sub 3}R3) within the N-terminal suppressor domains of IP{sub 3}R1{sub SUP} and IP{sub 3}R3{sub SUP} interact directly with their respective C-terminal fragments. Together with the accompanying paper (Yamazaki, H., Chan, J., Ikura, M., Michikawa, T., and Mikoshiba, K. (2010) J. Biol. Chem. 285, 36081-36091), we demonstrate that the single aromatic residue in this region (Tyr-167 in IP{sub 3}R1 and Trp-168 in IP{sub 3}R3) plays a critical role in the coupling between ligand binding and channel gating.

36 MATERIALS SCIENCE↗

Detecting and Blocking Network Attacks at Ultra High Speeds

Stateful, in-depth, in-line traffic analysis for intrusion detection and prevention has grown increasingly more difficult as the data rates of modern networks rise. One point in the design space for high-performance network analysis - pursued by a number of commercial products - is the use of sophisticated custom hardware. For very high-speed processing, such systems often cast the entire analysis process in ASICs. This project pursued a different architectural approach, which we term Shunting. Shunting marries a conceptually quite simple hardware device with an Intrusion Prevention System (IPS) running on commodity PC hardware. The overall design goal is was to keep the hardware both cheap and readily scalable to future higher speeds, yet also retain the unparalleled flexibility that running the main IPS analysis in a full general-computing environment provides. The Shunting architecture we developed uses a simple in-line hardware element that maintains several large state tables indexed by packet header fields, including IP/TCP flags, source and destination IP addresses, and connection tuples. The tables yield decision values the element makes on a packet-by-packet basis: forward the packet, drop it, or divert ('shunt') it through the IPS (the default). By manipulating table entries, the IPS can, on a fine-grained basis: (i) specify the traffic it wishes to examine, (ii) directly block malicious traffic, and (iii) 'cut through' traffic streams once it has had an opportunity to 'vet' them, or (iv) skip over large items within a stream before proceeding to further analyze it. For the Shunting architecture to yield benefits, it needs to operate in an environment for which the monitored network traffic has the property that - after proper vetting - much of it can be safely skipped. This property does not universally hold. For example, if a bank needs to examine all Web traffic involving its servers for regulatory compliance, then a monitor in front of one of the bank's server farms cannot safely omit a subset of the traffic from analysis. In this environment, Shunting cannot realize its main performance benefits, and the monitoring task likely calls for using custom hardware instead. However, in many other environments we find Shunting holds promise for delivering major performance gains. This arises due to the the widely documented 'heavy tail' nature of most forms of network traffic, which we might express as 'a few of the connections carry just about all the bytes.' The key additional insight is '... and very often for these few large connections, the very beginning of the connection contains nearly all the information of interest from a security analysis perspective.' We argue that this second claim holds because it is at the beginning of connections that authentication exchanges occur, data or file names and types are specified, request and reply status codes conveyed, and encryption is negotiated. Once these occur, we have seen most of the interesting facets of the dialog. Certainly the remainder of the connection might also yield some grist for analysis, but this is generally less likely, and thus if we want to lower analysis load at as small a loss as possible of information relevant to security analysis, we might best do so by skipping the bulk of large connections. In a different context, the 'Time Machine' work by Kornexl and colleagues likewise shows that in some environments we can realize major reductions in the volume of network traffic processed, by limiting the processing to the first 10-20 KB of each connection. As a concrete example, consider an IPS that monitors SSH traffic. When a new SSH connection arrives and the Shunt fails to find an entry for it in any of its tables (per-address, per-port, per-connection), it executes the default action of diverting the connection through the IPS. The IPS analyzes the beginning of the connection in this fashion. As long as it is satisified with the dialog, it reinjects the packets forwarded to it so that the connection can continue. If the connection successfully negotiates encryption, the IPS can no longer profitably analyze it, so it downloads a per-connection table entry to the Shunt specifying that the action for the connection in the future is 'forward.' For heavy-tailed connections, this means a very large majority of the connection's packets will now pass through the Shunt device without burdening the IPS with any further analysis load. On the other hand, if the IPS is dissatisfied with some element of the initial dialog, it downloads a 'drop' entry to terminate the connection. Note that by providing for reinjection, we can promote an intrusion detection system into an intrusion prevention system, one that does not merely detect attacks but can block them before they complete. Reinjection also allows the IPS to normalize traffic to remove ambiguities that attackers can leverage to evade the IPS.

99 GENERAL AND MISCELLANEOUS↗

Watching Electrons Transfer from Metals to Insulators using Two Photon Photoemission

Ultrafast angle-resolved two photon photoemission was used to study the dynamics and interfacial band structure of ultrathin films adsorbed onto Ag(111). Studies focused on the image potential state (IPS) in each system as a probe for measuring changes in electronic behavior in differing environments. The energetics and dynamics of the IPS at the toluene/Ag(111) interface are strongly dependent upon coverage. For a single monolayer, the first IPS is bound by 0.81 eV below the vacuum level and has a lifetime of 50 femtoseconds (fs). Further adsorption of toluene creates islands of toluene with an exposed wetting layer underneath. The IPS is then split into two peaks, one corresponding to the islands and one corresponding to the monolayer. The wetting layer IPS shows the same dynamics as the monolayer, while the lifetime of the islands increases exponentially with increasing thickness. Furthermore, the island IPS transitions from delocalized to localized within 500 fs, and electrons with larger parallel momenta decay much faster. Attempts were made using a stochastic model to extract the rates of localization and intraband cooling at differing momenta. In sexithiophene (6T) and dihexyl-sexithiophene (DH6T), the IPS was used as a probe to see if the nuclear motion of spectating side chains can interfere with molecular conduction. The energy and band mass of the IPS was measured for 6T and two geometries of DH6T on Ag(111). Electrons injected into the thicker coverages of DH6T grew exponentially heavier until they were completely localized by 230 fs, while those injected into 6T remained nearly free electron like. Based off of lifetime arguments and the density of defects, the most likely cause for the mass enhancement of the IPS in this system is small polaron formation caused by coupling of the electron to vibrations of the alkyl substituents. The energetic relaxation of the molecular adsorbate was also measured to be 20 meV/100 fs for the DH6T, and 0 meV/100 fs for the 6T. This relaxation is consistent with the localization of the charge creating a barrier for it moving from one lattice site to a neighboring one. Finally, the IPS was used to study the evolution of the surface band gap at the Mg/Ag(111) interface. The Mg(0001) surface band gap lies 1.6 eV below the Fermi level, and consequently shows no peak in the projected density of states for the IPS. A method for creating layer by layer growth of Mg on Ag(111) was determined using Auger Spectroscopy and low energy electron diffraction. By monitoring the decay of the intensity of the IPS versus coverage, it was determined that four layers of magnesium on Ag(111) is sufficient to completely eliminate the surface band gap

36 MATERIALS SCIENCE↗

Arabidopsis ABCG14 forms a homodimeric transporter for multiple cytokinins and mediates long-distance transport of isopentenyladenine-type cytokinins

Phytohormone cytokinins (CKs), primarily including trans-zeatin (tZ) and isopentenyladenine (iP) types, play critical roles in plant growth, development, and stress response. Long-distance transport of trans-zeatin (tZ)-type CKs has been well elucidated. However, long-distance transport of isopentenyladenine (iP)-type CKs remains unknown. Here, we demonstrated that the physiologically characterized ABC transporter AtABCG14 is also involved in long-distance transport of iP-type CKs. Biochemical characterization of AtABCG14 revealed that it forms homodimers and exhibits transporter properties towards multiple CKs, including iP and tZ types. AtABCG14 expression was induced by iP-type CKs in wild type and cyp735a1/a2 (cypDM) double mutant. The triple mutant atabcg14 cypDM exhibited more severe developmental phenotypes than atabcg14 and cypDM. CK quantification and 2 H 6 -iP isotope tracer experiment showed that the root-to-shoot transport of iP-type CKs was suppressed in atabcg14 cypDM. The reciprocal grafting of atabcg14 cypDM and cypDM revealed that AtABCG14 is responsible for the root xylem-loading and shoot phloem-distribution in the shootward transport of iP-type cytokinoins. Additionally, 2 H 6 -iP tracer experiment showed that the rootward transport of iP-type CKs was dependent on AtABCG14 expression in the roots. Collectively, our results demonstrate the long-distance circular transport of iP-type CKs mediated by AtABCG14 and provide new insights into the transport of CKs and other phytohormones.

59 BASIC BIOLOGICAL SCIENCES↗

Diverse Cd{sup II} coordination complexes derived from bromide isophthalic acid binding with auxiliary N-donor ligands

The coordination characteristics of 4-bromoisophthalic acid (4-Br-H{sub 2}ip) have been investigated in a series of Cd{sup II}-based frameworks. Hydrothermal reactions of Cd{sup II} salts and 4-Br-H{sub 2}ip together with flexible or semiflexible N-donor auxiliary ligands resulted in the formation of four three-dimensional coordination complexes with diverse structures: (Cd(bix){sub 0.5}(bix){sub 0.5}(4-Br-ip)]·H{sub 2}O){sub n} (1), [Cd(bbi){sub 0.5}(bbi){sub 0.5}(4-Br-ip)]{sub n} (2), ([Cd(btx){sub 0.5}(4-Br-ip)(H{sub 2}O)]·0.5CH{sub 3}OH·H{sub 2}O){sub n} (3) and ([Cd(bbt){sub 0.5}(4-Br-ip)(H{sub 2}O)]·3·5H{sub 2}O){sub n} (4). These compounds were characterized by elemental analyses, IR spectra, single-crystal and powder X-ray diffraction. They displayed diverse structures depending on the configuration of the 4-connected metal node, the coordination mode of the 4-Br-H{sub 2}ip, the coordination ability and conformationally flexibility of the N-donor auxiliary. Compound 1 exhibits 3-fold interpenetrated 6{sup 6} topology and compound 2 has a 4{sup 12} topology. Compounds 3–4 have similar 3D pillar-layered structures based on 3,4-connected binodal net with the Schläfli symbol of (4·3{sup 8}). The thermal stabilities and photoluminescence properties of them were discussed in detail. - Graphical abstract: Four 3D Cd{sup II} coordination complexes on the basis of 4-bromoisophthalic acid (4-Br-H{sub 2}ip) and two types of flexible (bbi, bbt) and semiflexible (bix, btx) N-donor ligands are prepared. They displayed diverse topology structures of 6{sup 6} (1), 4{sup 12} (2) and 4·3{sup 8} (3−4), depending on the configuration of the 4-connected metal node, the coordination mode of the 4-Br-H{sub 2}ip, the coordination ability and conformationally flexibility of the N-donor auxiliary ligand. - Highlights: • Four 3D Cd{sup II} coordination complexes based on 4-Br-H{sub 2}ip and flexible/semiflexible N-donor ligands have been synthesized. • They displayed diverse topology structures of 6{sup 6} for 1, 4{sup 12} for 2 and 4·3{sup 8} for 3–4. • The structural diversity depends on the configuration of 4-Br-H{sub 2}ip and the coordination behaviors of the auxiliary ligand.

36 MATERIALS SCIENCE↗

On negative induced polarization in frequency domain measurements

SUMMARY Induced polarization (IP) has been widely used to non-invasively characterize electrical conduction and polarization in the subsurface resulting from an applied electric field. Earth materials exhibit a lossy capacitance defined by a negative intrinsic phase in frequency-domain IP (FDIP) or a positive intrinsic chargeability in time-domain IP (TDIP). However, error-free positive apparent phase or negative apparent chargeability (i.e. negative IP effects) can occur in IP measurements over heterogeneous media. While negative IP effects in TDIP data sets have been discussed, no studies have addressed this topic in detail for FDIP measurements. We describe theory and numerical modelling to explain the origin of negative IP effects in FDIP measurements. A positive apparent phase may occur when a relatively high polarizability feature falls into negative sensitivity zones of complex resistivity measurements. The polarity of the apparent phase is determined by the distribution of subsurface intrinsic phase and resistivity, with the resistivity impacting the apparent phase polarity via its control on the sensitivity distribution. A physical explanation for the occurrence of positive apparent phase data is provided by an electric circuit model representing a four-electrode measurement. We also show that the apparent phase polarity will be frequency dependent when resistivity changes significantly with frequency (i.e. in the presence of significant IP effects). Consequently, negative IP effects manifest themselves in the shape of apparent phase spectra recorded with multifrequency (spectral IP) data sets. Our results imply that positive apparent phase measurements should be anticipated and should be retained during inversion and interpretation of single frequency and spectral IP data sets.

Geochemistry & Geophysics↗

Human gingival fibroblast feeder cells promote maturation of induced pluripotent stem cells into cardiomyocytes

Highlights: • HGF enhanced cardiac differentiation of iPS cells morphologically. • Contractility of iPS-CMs was significantly greater in the HGF feeder condition. • Amount of exogenous substance was minimum in the differentiation protocol. The use of human induced pluripotent stem (iPS) cells has been investigated in multiple regenerative medicine studies. However, although methods for efficient differentiation of iPS cells into heart tissues have been devised, it remains difficult to obtain cardiac tissue with high contractility. Herein, we established a method for differentiating iPS cells into highly contractile cardiomyocytes (CMs), and demonstrate that the use of human gingival fibroblasts (HGFs) as a feeder cells promotes maturation of iPS-derived CMs (iPS-CMs) in vitro. After CM differentiation of iPS cells, iPS-CMs showed increased mRNA expression of the CM specific maker cardiac troponin T (cTnT) in the absence and presence (on-feeder condition) of cocultured HGFs, and decreased expression of pluripotent markers was observed under both conditions. Protein expression of cTnT was also observed in immunocytochemical analyses, although on-feeder CMs showed comparatively robust sarcomere structure and significantly stronger contractility than feederless cardiomyocytes, suggesting that HGF feeder cells facilitate CM differentiation of iPS cells.

60 APPLIED LIFE SCIENCES↗

Characterization of beam ion loss in high poloidal beta regime on EAST

A critical issue for achieving the integrated operation of steady-state long-pulse high-confinement (H-mode) plasmas on experimental advanced superconducting tokamak (EAST) is to improve beam ion population confinement during neutral beam injection (NBI). To study the characterization of beam ion loss and improve beam ion confinement, the steady-state long pulse scenario discharges were conducted on EAST (β p $\geqslant$ 2.0, β N $\geqslant$ 1.7, q 95 $\geqslant$ 6.7 and H 98y2 $\geqslant$ 1.1) with NBI heating. Based on neutron yield, the beam voltage and line-averaged electron density were adjusted from 50 kV to 60 kV and 4.4 × 10 19 m –3 to 5.0 × 10 19 m –3 , respectively. The results show that the dominant mechanisms of beam ion loss are shine-through loss, prompt loss, and stochastic ripple loss. The shine-through loss fraction is determined by initial velocity, flight time and entire beam path. The change in prompt loss fraction is caused by the change in the deposition of beam ions. The change in stochastic ripple loss fraction is caused by the change in the initial fraction of trapped-confined ions. Detailed physics shows that the prompt loss fraction during counter-Ip injections (~45%) is far larger than during co-Ip injections (~5%) due to the finite orbit width. The lost ions are mainly deposited on the lower divertor or below the midplane since the direction of magnetic drift is vertical down. The orbit types of prompt loss during counter-Ip injections are mainly trapped-lost and ctr-passing lost. To minimize the prompt loss fraction during counter-Ip injections, a reversed Ip configuration (rev-Ip) discharge #94758 was conducted. The result suggests that the beam ion wall load fraction during counter-Ip tangential injection (~3%) is far lower than that in normal Ip configuration (nor-Ip) discharge #94820. It is also found that the confinement of beam ion population in the counter-Ip injection #94758 was greatly improved when compared to #94820. Finally, this study can provide unique support for the improvement of beam ion population confinement and for the performance evaluation of the NBI system on EAST and future tokamaks.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

In-Flight Operation of the Dawn Ion Propulsion System - The First Nine Months

The Dawn mission, part of NASA's Discovery Program, has as its goal the scientific exploration of the two most massive main-belt asteroids, Vesta and Ceres. The Dawn spacecraft was launched from Cape Canaveral Air Force Station on September 27, 2007 on a Delta-II 7925H-9.5 (Delta-II Heavy) rocket that placed the 1218 kg spacecraft into an Earth-escape trajectory. On-board the spacecraft is an ion propulsion system (IPS) which will provide most of the delta-V needed for heliocentric transfer to Vesta, orbit capture at Vesta, transfer to Vesta science orbits, departure and escape from Vesta, heliocentric transfer to Ceres, orbit capture at Ceres, and transfer to Ceres science orbits. The Dawn ion engine design is based on the design validated on NASA's Deep Space 1 mission. However, because of the very substantial (11 km/s) delta-V requirements for this mission Dawn requires two engines to complete its mission objectives. The power processor units (PPU), digital control and interface units (DCIU) slice boards and the xenon control assembly (XCA) are also based on the DS1 design. The DCIUs and thrust gimbal assemblies (TGA) were developed at the Jet Propulsion Laboratory. The spacecraft was provided by Orbital Sciences Corporation, Sterling, Virginia, and the mission is managed by and operated from the Jet Propulsion Laboratory. Dawn partnered with Germany, Italy and Los Alamos National Laboratory for the science instruments. The mission is led by the principal investigator, Dr. Christopher Russell, from the University of California, Los Angeles. The first 80 days after launch were dedicated to the initial checkout of the spacecraft prior to the initiation of long-term thrusting for the heliocentric transfer to Vesta. The IPS hardware, consisting of three ion thrusters and TGAs, two PPUs and DCIUs, xenon feed system, and spacecraft control software, was investigated extensively. Thrust measurements, roll torque measurements, pointing capabilities, control characteristics, and thermal behavior of the spacecraft and IPS were carefully evaluated. The Dawn IPS fully met all its initial checkout performance objectives. Deterministic thrusting for cruise began on December 17, 2007. Over the subsequent approximately 330 days the IPS will be operated virtually continuously at full power thrusting (approximately 91 mN) leading to a Mars flyby in February 2009. The encounter with Mars provides a gravity assist for a plane change and is the only source of post-launch delta-V apart from the IPS. Following the Mars gravity assist IPS will be operated for approximately one year at full power and for 1.3 years at throttled power levels leading to rendezvous with Vesta in August of 2011. Following nine months of orbital operations with IPS providing the propulsion needed for orbit capture, science orbit transfer and orbit maintenance and Vesta escape, Dawn will transit to Ceres with an expected arrival date of February 2015. As of June 16, 2008 the ion thrusters on Dawn have operated for close to 3,846 hours and have delivered nearly 1 km/s of delta-V to the spacecraft. Dawn IPS operation has been almost flawless during the initial checkout and six months of cruise. This paper provides an overview of Dawn's mission objectives, mission and system design, and the results of the post-launch Dawn IPS mission operations through June 2008

Garner, Charles E.↗

Internet protocol network mapper

A system for identifying IP ranges having a network address and a network address mask is provided. The system generates a collection of IP ranges. For each unique network address as defined by a maximum network address mask within provided IP addresses, the system adds to the collection an IP range for that unique network address. The added IP range may be defined by the unique network address and a network address mask that is set to the maximum network address mask. The system identifies groups of IP ranges of the collection to be represented by a combined IP range with a combined network address mask. For each group of IP ranges, the system removes from the collection the IP ranges within the group and adds to the collection the combined IP range with a network address and the combined network address mask.

Youd, David W.↗

A Scalable Interior‐Point Gauss–Newton Method for PDE‐Constrained Optimization With Bound Constraints

Here, we present a scalable approach to solve a class of partial differential equation (PDE)‐constrained optimization problems with bound constraints. This approach utilizes a robust full‐space interior‐point (IP)‐Gauss–Newton optimization method. To cope with the poorly‐conditioned IP‐Gauss–Newton saddle‐point linear systems that need to be solved approximately, once per optimization step, we propose two spectrally related preconditioners. These preconditioners leverage the limited informativeness of data in regularized PDE‐constrained optimization problems. A block Gauss–Seidel preconditioner is proposed for the GMRES‐based solution of the IP‐Gauss–Newton linear systems. It is shown, for a large‐class of PDE‐ and bound‐constrained optimization problems, that the spectrum of the block Gauss–Seidel preconditioned IP‐Gauss–Newton matrix is asymptotically independent of discretization and is not impacted by the ill‐conditioning that notoriously plagues interior‐point methods. We exploit symmetry of the IP‐Gauss–Newton linear systems and propose a regularization and log‐barrier Hessian preconditioner for the preconditioned conjugate gradient (PCG)‐based solution of the equivalent IP‐Gauss–Newton–Schur complement linear systems. The eigenvalues of the block Gauss–Seidel preconditioned IP‐Gauss–Newton matrix, that are not equal to one, are identical to the eigenvalues of the regularization and log‐barrier Hessian preconditioned Schur complement matrix. The scalability of the approach is demonstrated on two example problems. The numerical solution of these optimization problems is shown to require a discretization independent number of IP‐Gauss–Newton linear solves. Furthermore, the linear systems are solved in a discretization and IP ill‐conditioning independent number of preconditioned Krylov subspace iterations. The parallel scalability of the preconditioner, achieved via algebraic multigrid component solvers when applicable, and the aforementioned algorithmic scalability permits a parallel scalable means to compute solutions of a large class of PDE‐ and bound‐constrained problems.

PDE-constrained optimization↗

Trophoblast lineage cells derived from human induced pluripotent stem cells

Highlights: •Epithelial-like phenotype of trophoblast lineage cells derived from human iPS cells. •Trophoblast lineage cells derived from human iPS cells exhibit trophoblast function. •Trophoblasts from iPS cells provides a proof-of-concept in regenerative medicine. -- Abstract: Background: During implantation, the blastocyst trophectoderm attaches to the endometrial epithelium and continues to differentiate into all trophoblast subtypes, which are the major components of a placenta. Aberrant trophoblast proliferation and differentiation are associated with placental diseases. However, due to ethical and practical issues, there is almost no available cell or tissue source to study the molecular mechanism of human trophoblast differentiation, which further becomes a barrier to the study of the pathogenesis of trophoblast-associated diseases of pregnancy. In this study, our goal was to generate a proof-of-concept model for deriving trophoblast lineage cells from induced pluripotency stem (iPS) cells from human fibroblasts. In future studies the generation of trophoblast lineage cells from iPS cells established from patient’s placenta will be extremely useful for studying the pathogenesis of individual trophoblast-associated diseases and for drug testing. Methods and results: Combining iPS cell technology with BMP4 induction, we derived trophoblast lineage cells from human iPS cells. The gene expression profile of these trophoblast lineage cells was distinct from fibroblasts and iPS cells. These cells expressed markers of human trophoblasts. Furthermore, when these cells were differentiated they exhibited invasive capacity and placental hormone secretive capacity, suggesting extravillous trophoblasts and syncytiotrophoblasts. Conclusion: Trophoblast lineage cells can be successfully derived from human iPS cells, which provide a proof-of-concept tool to recapitulate pathogenesis of patient placental trophoblasts in vitro.

60 APPLIED LIFE SCIENCES↗

Structures of Fission Yeast Inositol Pyrophosphate Kinase Asp1 in Ligand-Free, Substrate-Bound, and Product-Bound States

Expression of the fission yeast Schizosaccharomyces pombe phosphate regulon is sensitive to the intracellular level of the inositol pyrophosphate signaling molecule 1,5-IP 8 . IP 8 dynamics are determined by Asp1, a bifunctional enzyme consisting of an N-terminal kinase domain and a C-terminal pyrophosphatase domain that catalyze IP 8 synthesis and catabolism, respectively. Here, we report structures of the Asp1 kinase domain, crystallized with two protomers in the asymmetric unit, one of which was complexed with ligands (ADPNP, ADP, or ATP; Mg 2+ or Mn 2+ ; IP 6 , 5-IP 7 , or 1,5-IP 8 ) and the other which was ligand-free. The ligand-free enzyme adopts an “open” conformation that allows ingress of substrates and egress of products. ADPNP, ADP, and ATP and associated metal ions occupy a deep phospho-donor pocket in the active site. IP 6 or 5-IP 7 engagement above the nucleotide favors adoption of a “closed” conformation, in which surface protein segments undergo movement and a disordered-to-ordered transition to form an inositol polyphosphate-binding site. In a structure mimetic of the kinase Michaelis complex, the anionic 5-IP 7 phosphates are encaged by an ensemble of nine cationic amino acids: Lys43, Arg223, Lys224, Lys260, Arg274, Arg285, Lys290, Arg293, and Lys341. Alanine mutagenesis of amino acids that contact the adenosine nucleoside of the ATP donor underscored the contributions of Asp258 interaction with the ribose 3'-OH and of Glu248 with adenine-N 6 . Changing Glu248 to Gln elicited a gain of function whereby the kinase became adept at using GTP as phosphate donor. Wild-type Asp1 kinase can utilize N 6 -benzyl-ATP as phosphate donor.

59 BASIC BIOLOGICAL SCIENCES↗

In-Flight Operation of the Dawn Ion Propulsion System Through Completion of the Final Orbit Around Dwarf Planet Ceres

The Dawn mission, part of NASA’s Discovery Program, has as its goal the scientific exploration of the two most massive main-belt objects, Vesta and Ceres. The Dawn spacecraft was launched from the Cape Canaveral Air Force Station on September 27, 2007 on a Delta-II 7925H- 9.5 (Delta-II Heavy) rocket that placed the 1218-kg spacecraft onto an Earth-escape trajectory. On-board the spacecraft is an ion propulsion system (IPS) developed at the Jet Propulsion Laboratory for the heliocentric transfer to Vesta, orbit capture at Vesta, transfer between Vesta science orbits, departure and escape from Vesta, heliocentric transfer to Ceres, orbit capture at Ceres, transfer between Ceres science orbits, and orbit maintenance maneuvers. Full-power thrusting from December 2007 through October 2008 was used to successfully target a Mars gravity assist flyby in February 2009 that provided an additional DV of 2.6 km/s. Deterministic thrusting for the heliocentric transfer to Vesta resumed in June 2009 and concluded with orbit capture at Vesta on July 16, 2011. From July 2011 through September 2012 the IPS was used to transfer to all the different science orbits at Vesta and to escape from Vesta orbit. Cruise for a rendezvous with Ceres began in August 2012 and completed in late December 2014. From December 2014 through June 2016 the IPS was used for transiting the spacecraft to all science orbits at Ceres including the final orbit for Dawn’s primary mission, called the low altitude mapping orbit (LAMO), a circular orbit at a mean altitude above Ceres of approximately 385 km. Dawn met or exceeded all pre-launch science requirements and Dawn's prime mission concluded on June 30, 2016. Dawn subsequently received NASA approval for two extended missions at Ceres, called XM1 and XM2. During XM1 IPS was used for orbit maintenance and to transit the spacecraft to several new, higher-altitude science orbits, ending in an elliptical orbit at a maximum altitude of approximately 38,000 km. In XM2, IPS operations included transiting the Dawn spacecraft to its final, highly elliptical orbit at Ceres ranging from 35 km perigee to 4,800 km apogee. Science data acquisition will continue in XM2 until the hydrazine is exhausted, which is expected to occur between August and October 2018. Dawn has successfully completed all science goals for both the primary and XM1 extended missions. To date the IPS has been operated for approximately 51,250 hours, consumed approximately 416 kg of xenon, and provided a delta-V of almost 11.5 km/s, a record for an on-board propulsion system. The IPS performance characteristics are close to the expected performance based on analysis and testing performed pre-launch. Dawn’s IPS continues to be fully operational as of June 2018. This paper provides an overview of Dawn’s mission objectives and the results of Dawn IPS mission operations for XM1, and XM2 through June 2018.

Rayman, Marc D.↗

Demonstrating imaging plate detector stacks for proton radiography using exploding pusher capsules

A new detector design has been fielded on the Omega-60 laser facility using a D 3 He backlighter capsule to radiograph a magnetized experiment. D 3 He capsules produce a low flux (~ 10 8 total yield in 4π) of protons requiring detectors with close-to single-particle sensitivity to be employed. The new detector stack consisted of both imaging plate (IP) and CR-39 to detect 14.7 MeV protons where, historically, only CR-39 has been used. IP is sensitive to significant contributions in signal from both x-rays and protons so additional filtering has to be added to attenuate the x-rays. Here, the signals and features observed from a single shot are detected by both IP and CR-39, giving confirmation that it is protons creating the signatures on the IP. Measurements of PSL/pixel are used to calculate approximate on-shot proton yields and agree with commonly measured yields. A second IP is used at the rear of the stack to measure, and subsequently remove, a background signal. The spatial resolution at the IP is limited, primarily, by a range of proton energies with varying deflections being recorded at the detector, causing potential ‘blurring’ of features. We find for this setup that the blurring effect is less than the smallest identifiable features observed at the detector, and therefore of minimal impact. A large benefit to this new stack design is that IP can be scanned and processed on much faster timescales than CR-39 allowing for prompt shot feedback. Future designs and modifications to the stack design fielded on this experiment could help improve the contrast of the radiograph on IP, as well as detecting protons produced at alternative energies.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Response functions of Fuji imaging plates to monoenergetic protons in the energy range 0.6-3.2 MeV

We have measured the responses of Fuji MS, SR, and TR imaging plates (IPs) to protons with energies ranging from 0.6 to 3.2 MeV. Monoenergetic protons were produced with the 3.5 MV AIFIRA (Applications Interdisciplinaires de Faisceaux d'Ions en Region Aquitaine) accelerator at the Centre d'Etudes Nucleaires de Bordeaux Gradignan (CENBG). The IPs were irradiated with protons backscattered off a tantalum target. We present the photo-stimulated luminescence response of the IPs together with the fading measurements for these IPs. A method is applied to allow correction of fading effects for variable proton irradiation duration. Using the IP fading corrections, a model of the IP response function to protons was developed. The model enables extrapolation of the IP response to protons up to proton energies of 10 MeV. Our work is finally compared to previous works conducted on Fuji TR IP response to protons.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Multireference configuration interaction calculations of the first six ionization potentials of the uranium atom

The first 6 ionization potentials (IPs) of the uranium atom have been calculated using multireference configuration interaction (MRCI+Q) with extrapolations to the complete basis set limit using new all-electron correlation consistent basis sets. The latter was carried out with the third-order Douglas-Kroll-Hess Hamiltonian. Correlation down through the 5s5p5d electrons has been taken into account, as well as contributions to the IPs due to the Lamb shift. Spin-orbit coupling contributions calculated at the 4-component Kramers restricted configuration interaction level, as well as the Gaunt term computed at the Dirac-Hartree-Fock level, were added to the best scalar relativistic results. The final ionization potentials are expected to be accurate to at least 5 kcal/mol (0.2 eV) and thus more reliable than the current experimental values of IP{sub 3} through IP{sub 6}.

74 ATOMIC AND MOLECULAR PHYSICS↗

Detailed characterization of the LLNL imaging proton spectrometer

Ultra-intense short pulse lasers incident on solid targets (e.g., thin Au foils) produce well collimated, broad-spectrum proton beams. These proton beams can be used to characterize magnetic fields, electric fields, and density gradients in high energy-density systems. The LLNL-Imaging Proton Spectrometer (L-IPS) was designed and built [H. Chen et al., Rev. Sci. Instrum. 81, 10D314 (2010)] for use with such laser produced proton beams. The L-IPS has an energy range of 50 keV-40 MeV with a resolving power (E/dE) of about 275 at 1 MeV and 21 at 20 MeV, as well as a single spatial imaging axis. In order to better characterize the dispersion and imaging capability of this diagnostic, a 3D finite element analysis solver is used to calculate the magnetic field of the L-IPS. Particle trajectories are then obtained via numerical integration to determine the dispersion relation of the L-IPS in both energy and angular space.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗