Successful kinetic impact into an asteroid for planetary defence.

Although no known asteroid poses a threat to Earth for at least the next century, the catalogue of near-Earth asteroids is incomplete for objects whose impacts would produce regional devastation1,2. Several approaches have been proposed to potentially prevent an asteroid impact with Earth by deflecting or disrupting an asteroid1-3. A test of kinetic impact technology was identified as the highest-priority space mission related to asteroid mitigation1. NASA's Double Asteroid Redirection Test (DART) mission is a full-scale test of kinetic impact technology. The mission's target asteroid was Dimorphos, the secondary member of the S-type binary near-Earth asteroid (65803) Didymos. This binary asteroid system was chosen to enable ground-based telescopes to quantify the asteroid deflection caused by the impact of the DART spacecraft4. Although past missions have utilized impactors to investigate the properties of small bodies5,6, those earlier missions were not intended to deflect their targets and did not achieve measurable deflections. Here we report the DART spacecraft's autonomous kinetic impact into Dimorphos and reconstruct the impact event, including the timeline leading to impact, the location and nature of the DART impact site, and the size and shape of Dimorphos. The successful impact of the DART spacecraft with Dimorphos and the resulting change in the orbit of Dimorphos7 demonstrates that kinetic impactor technology is a viable technique to potentially defend Earth if necessary.

Structure of the catalytic domain of the Salmonella virulence factor SseI.

SseI is secreted into host cells by Salmonella and contributes to the establishment of systemic infections. The crystal structure of the C-terminal domain of SseI has been solved to 1.70 Å resolution, revealing it to be a member of the cysteine protease superfamily with a catalytic triad consisting of Cys178, His216 and Asp231 that is critical to its virulence activities. Structure-based analysis revealed that SseI is likely to possess either acyl hydrolase or acyltransferase activity, placing this virulence factor in the rapidly growing class of enzymes of this family utilized by bacterial pathogens inside eukaryotic cells.

Comparison of Deep Space Navigation Using Optical Imaging, Pulsar Time-of-Arrival Tracking, and/or Radiometric Tracking.

Recent advances with space navigation technologies developed by NASA in space-based atomic clocks and pulsar X-ray navigation, combined with past successes in autonomous navigation using optical imaging, brings to the forefront the need to compare space navigation using optical, radiometric, and pulsar-based measurements using a common set of assumptions and techniques. This review article examines these navigation data types in two different ways. First, a simplified deep space orbit determination problem is posed that captures key features of the dynamics and geometry, and then each data type is characterized for its ability to solve for the orbit. The data types are compared and contrasted using a semi-analytical approach with geometric dilution of precision techniques. The results provide useful parametric insights into the strengths of each data type. In the second part of the paper, a high-fidelity, Monte Carlo simulation of a Mars cruise, approach, and entry navigation problem is studied. The results found complement the semi-analytic results in the first part, and illustrate specific issues such as each data type's quantitative impact on solution accuracy and their ability to support autonomous delivery to a planet.

Autonomous Exploration of Small Bodies Toward Greater Autonomy for Deep Space Missions.

Autonomy is becoming increasingly important for the robotic exploration of unpredictable environments. One such example is the approach, proximity operation, and surface exploration of small bodies. In this article, we present an overview of an estimation framework to approach and land on small bodies as a key functional capability for an autonomous small-body explorer. We use a multi-phase perception/estimation pipeline with interconnected and overlapping measurements and algorithms to characterize and reach the body, from millions of kilometers down to its surface. We consider a notional spacecraft design that operates across all phases from approach to landing and to maneuvering on the surface of the microgravity body. This SmallSat design makes accommodations to simplify autonomous surface operations. The estimation pipeline combines state-of-the-art techniques with new approaches to estimating the target's unknown properties across all phases. Centroid and light-curve algorithms estimate the body-spacecraft relative trajectory and rotation, respectively, using a priori knowledge of the initial relative orbit. A new shape-from-silhouette algorithm estimates the pole (i.e., rotation axis) and the initial visual hull that seeds subsequent feature tracking as the body gets more resolved in the narrow field-of-view imager. Feature tracking refines the pole orientation and shape of the body for estimating initial gravity to enable safe close approach. A coarse-shape reconstruction algorithm is used to identify initial landable regions whose hazardous nature would subsequently be assessed by dense 3D reconstruction. Slope stability, thermal, occlusion, and terra-mechanical hazards would be assessed on densely reconstructed regions and continually refined prior to landing. We simulated a mission scenario for approaching a hypothetical small body whose motion and shape were unknown a priori, starting from thousands of kilometers down to 20 km. Results indicate the feasibility of recovering the relative body motion and shape solely relying on onboard measurements and estimates with their associated uncertainties and without human input. Current work continues to mature and characterize the algorithms for the last phases of the estimation framework to land on the surface.

Use of a bacteriophage lysin to identify a novel target for antimicrobial development.

We identified an essential cell wall biosynthetic enzyme in Bacillus anthracis and an inhibitor thereof to which the organism did not spontaneously evolve measurable resistance. This work is based on the exquisite binding specificity of bacteriophage-encoded cell wall-hydrolytic lysins, which have evolved to recognize critical receptors within the bacterial cell wall. Focusing on the B. anthracis-specific PlyG lysin, we first identified its unique cell wall receptor and cognate biosynthetic pathway. Within this pathway, one biosynthetic enzyme, 2-epimerase, was required for both PlyG receptor expression and bacterial growth. The 2-epimerase was used to design a small-molecule inhibitor, epimerox. Epimerox prevented growth of several Gram-positive pathogens and rescued mice challenged with lethal doses of B. anthracis. Importantly, resistance to epimerox was not detected (<10(-11) frequency) in B. anthracis and S. aureus. These results describe the use of phage lysins to identify promising lead molecules with reduced resistance potential for antimicrobial development.

Discovery of Novel Putative Inhibitors of UDP-GlcNAc 2-Epimerase as Potent Antibacterial Agents.

We present the discovery and optimization of a novel series of inhibitors of bacterial UDP-N-acetylglucosamine 2-epimerase (called 2-epimerase in this paper). Starting from virtual screening hits, the activity of various inhibitory molecules was optimized using a combination of structure-based and rational design approaches. We successfully designed and identified a 2-epimerase inhibitor (compound 12-ES-Na, that we named Epimerox) which blocked the growth of methicillin-resistant Staphylococcus aureus (MRSA) at 3.9 µM MIC (minimum inhibitory concentration) and showed potent broad-range activity against all Gram-positive bacteria that were tested. Additionally a microplate coupled assay was performed to further confirm that the 2-epimerase inhibition of Epimerox was through a target-specific mechanism. Furthermore, Epimerox demonstrated in vivo efficacy and had a pharmacokinetic profile that is consonant with it being developed into a promising new antibiotic agent for treatment of infections caused by Gram-positive bacteria.

A structural basis for the allosteric regulation of non-hydrolysing UDP-GlcNAc 2-epimerases.

The non-hydrolysing bacterial UDP-N-acetylglucosamine 2-epimerase (UDP-GlcNAc 2-epimerase) catalyses the conversion of UDP-GlcNAc into UDP-N-acetylmannosamine, an intermediate in the biosynthesis of several cell-surface polysaccharides. This enzyme is allosterically regulated by its substrate UDP-GlcNAc. The structure of the ternary complex between the Bacillus anthracis UDP-GlcNAc 2-epimerase, its substrate UDP-GlcNAc and the reaction intermediate UDP, showed direct interactions between UDP and its substrate, and between the complex and highly conserved enzyme residues, identifying the allosteric site of the enzyme. The binding of UDP-GlcNAc is associated with conformational changes in the active site of the enzyme. Kinetic data and mutagenesis of the highly conserved UDP-GlcNAc-interacting residues confirm their importance in the substrate binding and catalysis of the enzyme. This constitutes the first example to our knowledge, of an enzymatic allosteric activation by direct interaction between the substrate and the allosteric activator.

The pH dependence of heme pocket hydration and ligand rebinding kinetics in photodissociated carbonmonoxymyoglobin.

We monitored the occupancy of a functionally important non-coordinated water molecule in the distal heme pocket of sperm whale myoglobin over the pH range 4.3-9.4. Water occupancy was assessed by using time-resolved spectroscopy to detect the perturbation of the heme visible band absorption spectrum caused by water entry after CO photodissociation ( Goldbeck, R. A., Bhaskaran, S., Ortega, C., Mendoza, J. L., Olson, J. S., Soman, J., Kliger, D. S., and Esquerra, R. M. (2006) Proc. Natl. Acad. Sci. U. S. A. 103, 1254-1259 ). We found that the water occupancy observed during the time interval between ligand photolysis and diffusive recombination decreased by nearly 20% as the pH was lowered below 6. This decrease accounted for most of the concomitant increase in the observed CO bimolecular recombination rate constant, as the lower water occupancy presented a smaller kinetic barrier to CO entry into the pocket at lower pH. These results were consistent with a model in which the distal histidine, which stabilizes the water molecule within the distal pocket by accepting a hydrogen bond, tends to swing out of the pocket upon protonation and destabilize the water occupancy at low pH. Extrapolation of this model to lower pH suggests that the additional increase in ligand association rate constant observed previously in stopped-flow studies at pH 3 may also be due in part to reduced distal water occupancy concomitant with further His64 protonation and coupled protein conformational change.

Designer bugs: structural engineering to build a better mouse model.

Many animal models of bacterial diseases are hampered by differences in tissue tropism and the course of pathogenesis. In a recent issue of Cell, by rationally mutating a surface invasion protein (InlA) to have higher binding affinity for its cognate host receptor (E-cadherin), Wollert et al. were able to "murinize"Listeria monocytogenes, creating a strain capable of invading intestinal epithelial cells in mice, mimicking the route of infection in humans.

Water and ligand entry in myoglobin: assessing the speed and extent of heme pocket hydration after CO photodissociation.

A previously undescribed spectrokinetic assay for the entry of water into the distal heme pocket of wild-type and mutant myoglobins is presented. Nanosecond photolysis difference spectra were measured in the visible bands of sperm whale myoglobin as a function of distal pocket mutation and temperature. A small blue shift in the 560-nm deoxy absorption peak marked water entry several hundred nanoseconds after CO photodissociation. The observed rate suggests that water entry is rate-limited by the escape of internal dissociated CO. The heme pocket hydration and geminate recombination yields were found to be the primary factors controlling the overall bimolecular association rate constants for CO binding to the mutants studied. The kinetic analysis provides estimates of 84%, 60%, 40%, 0%, and 99% for the steady-state hydrations of wild-type, H64Q, H64A, H64L, and V68F deoxymyoglobin, respectively. The second-order rate constants for CO and H(2)O entry into the empty distal pocket of myoglobin are markedly different, 8 x 10(7) and 2 x 10(5) M(-1).s(-1), respectively, suggesting that hydrophobic partitioning of the apolar gas from the aqueous phase into the relatively apolar protein interior lowers the free energy barrier for CO entry.