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At least 127 records · Page 7

Structural basis for C-degron selectivity across KLHDCX family E3 ubiquitin ligases

Abstract Specificity of the ubiquitin-proteasome system depends on E3 ligase-substrate interactions. Many such pairings depend on E3 ligases binding to peptide-like sequences - termed N- or C-degrons - at the termini of substrates. However, our knowledge of structural features distinguishing closely related C-degron substrate-E3 pairings is limited. Here, by systematically comparing ubiquitylation activities towards a suite of common model substrates, and defining interactions by biochemistry, crystallography, and cryo-EM, we reveal principles of C-degron recognition across the KLHDCX family of Cullin-RING ligases (CRLs). First, a motif common across these E3 ligases anchors a substrate’s C-terminus. However, distinct locations of this C-terminus anchor motif in different blades of the KLHDC2, KLHDC3, and KLHDC10 β-propellers establishes distinct relative positioning and molecular environments for substrate C-termini. Second, our structural data show KLHDC3 has a pre-formed pocket establishing preference for an Arg or Gln preceding a C-terminal Gly, whereas conformational malleability contributes to KLHDC10’s recognition of varying features adjacent to substrate C-termini. Finally, additional non-consensus interactions, mediated by C-degron binding grooves and/or by distal propeller surfaces and substrate globular domains, can substantially impact substrate binding and ubiquitylatability. Overall, the data reveal combinatorial mechanisms determining specificity and plasticity of substrate recognition by KLDCX-family C-degron E3 ligases.

Science & Technology - Other Topics↗

Pittsburgh Public School District / Carnegie Mellon University Robotics Team Participation in the US First Competition

FIRST, For Inspiration and Recognition of Science and Technology, is an international program designed to encourage junior and senior high school students to participate in science and technology related activities. FIRST attempts to increase enthusiasm for technology by providing a competitive environment in which to demonstrate robotics technology designed for a particular set of tasks. Carnegie Mellon University provided student members of the project the opportunity to complete the design, construction, testing, and operation of a robot. Electrical, mechanical, and programming skills were stressed, with both adult and senior students acting as mentors for more junior members. Teamwork and integration was also stressed in order to provide students with a realistic feel for project-based work. Finally, an emphasis was placed on recruiting students with greater difficulty in entering technological fields: girls and ethnic minorities and students leaning toward humanities (especially art). Carnegie Mellon built a relationship with Taylor Allderdice High School that lasted four years. For four years, the success of the project increased each year. Each term, the students successfully designed and built a working robot that could fully participate in the competition. The enthusiasm of the students has been the cornerstone of the recruit of new students, keeping the project growing and vital. Carnegie Mellon's participation with Allderdice has been an overall great success.

Stroupe, Ashley↗

NASA Johnson Space Center Usability Testing and Analysis Facility (UTAF) Overview

The Usability Testing and Analysis Facility (UTAF) is part of the Space Human Factors Laboratory at the NASA Johnson Space Center in Houston, Texas. The facility provides support to the Office of Biological and Physical Research, the Space Shuttle Program, the International Space Station Program, and other NASA organizations. In addition, there are ongoing collaborative research efforts with external businesses and universities. The UTAF provides human factors analysis, evaluation, and usability testing of crew interfaces for space applications. This includes computer displays and controls, workstation systems, and work environments. The UTAF has a unique mix of capabilities, with a staff experienced in both cognitive human factors and ergonomics. The current areas of focus are: human factors applications in emergency medical care and informatics; control and display technologies for electronic procedures and instructions; voice recognition in noisy environments; crew restraint design for unique microgravity workstations; and refinement of human factors processes. This presentation will provide an overview of ongoing activities, and will address how the projects will evolve to meet new space initiatives.

Whitmore, M.↗

NASA Johnson Space Center Usability Testing and Analysis Facility (WAF) Overview

The Usability Testing and Analysis Facility (UTAF) is part of the Space Human Factors Laboratory at the NASA Johnson Space Center in Houston, Texas. The facility provides support to the Office of Biological and Physical Research, the Space Shuttle Program, the International Space Station Program, and other NASA organizations. In addition, there are ongoing collaborative research efforts with external businesses and universities. The UTAF provides human factors analysis, evaluation, and usability testing of crew interfaces for space applications. This includes computer displays and controls, workstation systems, and work environments. The UTAF has a unique mix of capabilities, with a staff experienced in both cognitive human factors and ergonomics. The current areas of focus are: human factors applications in emergency medical care and informatics; control and display technologies for electronic procedures and instructions; voice recognition in noisy environments; crew restraint design for unique microgravity workstations; and refinement of human factors processes. This presentation will provide an overview of ongoing activities, and will address how the projects will evolve to meet new space initiatives.

Whitmore, M.↗

DNA in a Tunnel: A Comfy Spot for Recognition - or -The Structure of BsoBI Complexed with DNA. What can we Learn about Function via Structure Determination and how can this be Applied to Bone or Muscle Biology?

The structure and function of a biologically active molecule are related. To understand its function, it is necessary (but not always sufficient) to know the structure of the molecule. There are many ways of relating the molecular function with the structure. Mutation analysis can identify pertinent amino acids of an enzyme, or alternatively structure comparison of the of two similar molecules with different function may lead to understanding which parts are responsible for a functional aspect, or a series of "structural cartoons" - enzyme structure, enzyme plus substrate, enzyme with transition state analog, and enzyme with product - may give insight in the function of a molecule. As an example we will discuss the structure and function of the restriction enzyme BsoBI from Bacillus stearothemzophilus in complex with its cognate DNA. The enzyme forms a unique complex with DNA in that it completely encircles the DNA. The structure reveals the enzyme-DNA contacts, how the DNA is distorted compared with the canonical forms, and elegantly shows how two distinct DNA sequences can be recognized with the same efficiency. Based on the structure we may also propose a hypothesis how the enzymatic mechanism works. The knowledge gained thru studies such as this one can be used to alter the function by changing the molecular structure. Usually this is done by design of inhibitors specifically active against and fitting into an active site of the enzyme of choice. In the case of BsoBI one of the objectives of the study was to alter the enzyme specificity. In bone biology there are many candidates available for molecular study in order to explain, alter, or (temporarily) suspend activity. For example, the understanding of a pathway that negatively regulates bone formation may be a good target for drug design to stimulate bone formation and have good potential as the basis for new countermeasures against bone loss. In principle the same approach may aid muscle atrophy, radiation damage, immune response changes and other risks identified for long-duration Space travel.

vanderWoerd, Mark↗

Acting to gain information

This report is concerned with agents that act to gain information. In previous work, we developed agent models combining qualitative modeling with real-time control. That work, however, focused primarily on actions that affect physical states of the environment. The current study extends that work by explicitly considering problems of active information-gathering and by exploring specialized aspects of information-gathering in computational perception, learning, and language. In our theoretical investigations, we analyzed agents into their perceptual and action components and identified these with elements of a state-machine model of control. The mathematical properties of each was developed in isolation and interactions were then studied. We considered the complexity dimension and the uncertainty dimension and related these to intelligent-agent design issues. We also explored active information gathering in visual processing. Working within the active vision paradigm, we developed a concept of 'minimal meaningful measurements' suitable for demand-driven vision. We then developed and tested an architecture for ongoing recognition and interpretation of visual information. In the area of information gathering through learning, we explored techniques for coping with combinatorial complexity. We also explored information gathering through explicit linguistic action by considering the nature of conversational rules, coordination, and situated communication behavior.

Rosenchein, Stanley J.↗

Evolution of the Mobile Information SysTem (MIST)

The Mobile Information SysTem (MIST) had its origins in the need to determine whether commercial off the shelf (COTS) technologies could improve intervehicular activities (IVA) on International Space Station (ISS) crew maintenance productivity. It began with an exploration of head mounted displays (HMDs), but quickly evolved to include voice recognition, mobile personal computing, and data collection. The unique characteristic of the MIST lies within its mobility, in which a vest is worn that contains a mini-computer and supporting equipment, and a headband with attachments for a HMD, lipstick camera, and microphone. Data is then captured directly by the computer running Morae(TM) or similar software for analysis. To date, the MIST system has been tested in numerous environments such as two parabolic flights on NASA's C-9 microgravity aircraft and several mockup facilities ranging from ISS to the Altair Lunar Sortie Lander. Functional capabilities have included its lightweight and compact design, commonality across systems and environments, and usefulness in remote collaboration. Human Factors evaluations of the system have proven the MIST's ability to be worn for long durations of time (approximately four continuous hours) with no adverse physical deficits, moderate operator compensation, and low workload being reported as measured by Corlett Bishop Discomfort Scale, Cooper-Harper Ratings, and the NASA Total Workload Index (TLX), respectively. Additionally, through development of the system, it has spawned several new applications useful in research. For example, by only employing the lipstick camera, microphone, and a compact digital video recorder (DVR), we created a portable, lightweight data collection device. Video is recorded from the participants point of view (POV) through the use of the camera mounted on the side of the head. Both the video and audio is recorded directly into the DVR located on a belt around the waist. This data is then transferred to another computer for video editing and analysis. Another application has been discovered using simulated flight, in which, a kneeboard is replaced with mini-computer and the HMD to project flight paths and glide slopes for lunar ascent. As technologies evolve, so will the system and its application for research and space system operations.

Litaker, Harry L., Jr.↗

High-school Student Teams in a National NASA Microgravity Science Competition

The Dropping In a Microgravity Environment or DIME competition for high-school-aged student teams has completed the first year for nationwide eligibility after two regional pilot years. With the expanded geographic participation and increased complexity of experiments, new lessons were learned by the DIME staff. A team participating in DIME will research the field of microgravity, develop a hypothesis, and prepare a proposal for an experiment to be conducted in a NASA microgravity drop tower. A team of NASA scientists and engineers will select the top proposals and then the selected teams will design and build their experiment apparatus. When completed, team representatives will visit NASA Glenn in Cleveland, Ohio to operate their experiment in the 2.2 Second Drop Tower and participate in workshops and center tours. NASA participates in a wide variety of educational activities including competitive events. There are competitive events sponsored by NASA (e.g. NASA Student Involvement Program) and student teams mentored by NASA centers (e.g. For Inspiration and Recognition of Science and Technology Robotics Competition). This participation by NASA in these public forums serves to bring the excitement of aerospace science to students and educators.Researchers from academic institutions, NASA, and industry utilize the 2.2 Second Drop Tower at NASA Glenn Research Center in Cleveland, Ohio for microgravity research. The researcher may be able to complete the suite of experiments in the drop tower but many experiments are precursor experiments for spaceflight experiments. The short turnaround time for an experiment's operations (45 minutes) and ready access to experiment carriers makes the facility amenable for use in a student program. The pilot year for DIME was conducted during the 2000-2001 school year with invitations sent out to Ohio- based schools and organizations. A second pilot year was conducted during the 2001-2002 school year for teams in the six-state region of Illinois, Indiana, Michigan, Minnesota, Ohio, and Wisconsin. The third year for DIME was conducted during the 2002-2003 school year for teams from the fifty United States, the District of Columbia, and Puerto Rico. An annual national DIME program is planned for the foreseeable future. Presented in this paper will be a description of DIME, an overview of the planning and execution of such a program, results from the first three years, and lessons learned from the first national competition.

DeLombard, Richard↗

NASA Johnson Space Center Usability Testing and Analysis facility (UTAF) Overview

The Usability Testing and Analysis Facility (UTAF) is part of the Space Human Factors Laboratory at the NASA Johnson Space Center in Houston, Texas. The facility performs research for NASA's HumanSystems Integration Program, under the HumanSystems Research and Technology Division. Specifically, the UTAF provides human factors support for space vehicles, including the International Space Station, the Space Shuttle, and the forthcoming Crew Exploration Vehicle. In addition, there are ongoing collaborative research efforts with external corporations and universities. The UTAF provides human factors analysis, evaluation, and usability testing of crew interfaces for space applications. This includes computer displays and controls, workstation systems, and work environments. The UTAF has a unique mix of capabilities, with a staff experienced in both cognitive human factors and ergonomics. The current areas of focus are: human factors applications in emergency medical care and informatics; control and display technologies for electronic procedures and instructions; voice recognition in noisy environments; crew restraint design for unique microgravity workstations; and refinement of human factors processes and requirements. This presentation will provide an overview of ongoing activities, and will address how the UTAF projects will evolve to meet new space initiatives.

Whitmore, Mihriban↗

Risks of Increased Earth Independence

As human space exploration begins to extend beyond the immediate vicinity of Earth, the ability of expertise on the ground to support operations will progressively decrease. Ground control expertise has been the primary countermeasure preventing loss of life and mission over the past sixty years and it will be gradually stripped away as expeditions reach further into space. The large, flexible and adaptive teams of experts on the ground, provide not only engineering analysis and problem-solving but also greatly increased work capacity. Monitoring of the large and fast moving stream of telemetry data is carried out around the clock by 20-30 flight controllers per shift. Analysis of that data and troubleshooting is carried out by an additional 50-100 engineers per shift. Artificial intelligence capabilities will need to be part of the solution but will not the entire solution. As progress continues to be made on intelligent systems, especially those for use in complex, dynamic environments where humans will remain a part of the activity, there is an ever increasing need to focus on how those systems will interact with the humans. Although capabilities such as natural language processing and facial recognition have become common place, even basic aspects of problem-solving, causal reasoning and generative decision-making remain well-beyond of our current capabilities. Advanced data visualization, procedure execution support, and new training approaches will be needed to close the gap between what is currently provided by experts on the ground and what the crew will need to do in increasingly autonomous ways with greater distance from Earth.

human-systems integration architecture↗

Membership generation using multilayer neural network

There has been intensive research in neural network applications to pattern recognition problems. Particularly, the back-propagation network has attracted many researchers because of its outstanding performance in pattern recognition applications. In this section, we describe a new method to generate membership functions from training data using a multilayer neural network. The basic idea behind the approach is as follows. The output values of a sigmoid activation function of a neuron bear remarkable resemblance to membership values. Therefore, we can regard the sigmoid activation values as the membership values in fuzzy set theory. Thus, in order to generate class membership values, we first train a suitable multilayer network using a training algorithm such as the back-propagation algorithm. After the training procedure converges, the resulting network can be treated as a membership generation network, where the inputs are feature values and the outputs are membership values in the different classes. This method allows fairly complex membership functions to be generated because the network is highly nonlinear in general. Also, it is to be noted that the membership functions are generated from a classification point of view. For pattern recognition applications, this is highly desirable, although the membership values may not be indicative of the degree of typicality of a feature value in a particular class.

Kim, Jaeseok↗

Sensor Web in Antarctica: Developing an Intelligent, Autonomous Platform for Locating Biological Flourishes in Cryogenic Environments

The most rigorous tests of the ability to detect extant life will occur where biotic activity is limited by severe environmental conditions. Cryogenic environments are among the most severe-the energy and nutrients needed for biological activity are in short supply while the climate itself is actively destructive to biological mechanisms. In such settings biological activity is often limited to brief flourishes, occurring only when and where conditions are at their most favorable. The closer that typical regional conditions approach conditions that are actively hostile , the more widely distributed biological blooms will be in both time and space. On a spatial dimension of a few meters or a time dimension of a few days, biological activity becomes much more difficult to detect. One way to overcome this difficulty is to establish a Sensor Web that can monitor microclimates over appropriate scales of time and distance, allowing a continuous virtual presence for instant recognition of favorable conditions. A more sophisticated Sensor Web, incorporating metabolic sensors, can effectively meet the challenge to be in "the right place in the right time". This is particularly of value in planetary surface missions, where limited mobility and mission timelines require extremely efficient sample and data acquisition. Sensor Webs can be an effective way to fill the gap between broad scale orbital data collection and fine-scale surface lander science. We are in the process of developing an intelligent, distributed and autonomous Sensor Web that will allow us to monitor microclimate under severe cryogenic conditions, approaching those extant on the surface of Mars. Ultimately this Sensor Web will include the ability to detect and/or establish limits on extant microbiological activity through incorporation of novel metabolic gas sensors. Here we report the results of our first deployment of a Sensor Web prototype in a previously unexplored high altitude East Antarctic Plateau "micro-oasis" at the MacAlpine Hills, Law Glacier, Antarctica.

Delin, K. A.↗

Pantex Plant Ogallala Aquifer and Perched Groundwater Contingency Plan

The Pantex Plant Ogallala Aquifer and Perched Groundwater Contingency Plan has been developed in accordance with the requirements identified in the: • Interagency Agreement for the Pantex Superfund Site, Article 8.5 Work to be Performed, • Compliance Plan Provision of Hazardous Waste Permit No. 50284, and • Record of Decision for Groundwater, Soil, and Associated Media, Pantex Plant. A Long‐Term Monitoring System Design has been designed to monitor conditions in the perched groundwater including changes in the perched aquifer as a result of implementing the response actions. Monitoring is required for verifying the effectiveness of perched groundwater response actions (i.e., conditions in the perched aquifer are being affected as intended) and for confirming that the perched aquifer and Ogallala Aquifer characterization as defined in the Resource Conservation and Recovery Act Facility Investigation Report and the Corrective Measure Studies/Feasibility Study remains accurate. If monitoring results obtained through the monitoring network identify an unexpected condition or deviation, contingent actions will be considered and implemented as necessary to ensure continued protection of the Ogallala Aquifer and human health and the environment. Potential deviations to expected technology performance may be encountered for each of the four primary response actions that compose the selected remedy for perched groundwater; Playa 1 Pump and Treat System, Southeast Area Pump and Treat System, Southeast Area In‐Situ Bioremediation System (comprised of the Southeast In‐Situ Bioremediation System Original System, Southeast Area In‐Situ Bioremediation System Extension System, Offsite In‐Situ Bioremediation System, Perchlorate/Chromium ISB, Northeast ISB and County Road 8 ISB), and Zone 11 In‐Situ Bioremediation System. Monitoring will also be conducted to determine if there are deviations to the expected characterization, e.g., contaminants not expected as a result of the RCRA Facility Investigation characterization. Deviations to expected conditions in the Ogallala Aquifer could also be encountered if the response actions in the perched groundwater are not performing as expected, i.e., preventing contaminants from migrating to the Ogallala Aquifer. Currently, Pantex has begun investigation of detections of high explosives above groundwater protection standards in wells on the Texas Tech University property and a plume that is moving to the northeast from that area. Due to those detections, this Plan recognizes the fact that future detections in the Ogallala will be focused on first‐ time detections of analytes. After a remedy is determined, this Plan will require modification to address-deviations and contingent actions. This Plan was developed to identify the contingent actions necessary to mitigate impacts resulting from deviations to site conditions or response action performance. The Plan defines the environmental problem being addressed by the response actions, clarifies the expected conditions and objectives of the response actions, and identifies the potential deviations to the response actions (due to site conditions or technology performance) that could be encountered. The deviations were evaluated to determine the likelihood of occurrence, potential impact, and time to respond to avoid impact. The Plan also identifies the monitoring outlined in the Long‐Term Monitoring System Design Report (Consolidated Nuclear Security, 2024) and Sampling Analysis Plan (PanTeXas Deterrence, 2024) that will be used to detect the deviations. Lastly, the Plan specifies the contingent actions that could be implemented in response to the deviations. Because each response focuses on a discrete portion of the perched aquifer and contaminant plume, each response action has a different set of expected conditions, and therefore differing impacts from deviations to the site and technology expectations. As a result, the contingent actions are identified for each response action and potential deviation including specific constituents, location, and conditions. If deviations are encountered that impact the ability of the response action to meet performance objectives, the contingent actions will be focused on ensuring the response action can meet the performance objective. Contingent actions may be implemented as interim actions (ISMs/removal actions) in accordance with the Record of Decision, Interagency Agreement, and Hazardous Waste Permit‐50284, if warranted by the specific circumstances. For deviations to site characterization expected conditions, the contingent action will focus on determination of the source of the deviation, determination of the appropriate response, and evaluation of additional work to be completed. However, if the deviation to characterization impacts the performance of the response action, the contingent action will again focus on ensuring performance objectives can be met. Early source term removals and cleanup actions have been implemented to protect the Ogallala Aquifer. Because of these actions and based on modeling results, the expected conditions in the Ogallala Aquifer are that constituents of concern will not be detected above the Groundwater Protection Standards (GWPSs) nor will they reach potential points of exposure above the GWPS. The primary deviation of concern for the Ogallala is if constituents are detected in the Ogallala Aquifer near or above GWPSs. If it occurs, this change in expected conditions would require further evaluation of site and contaminant characteristics to determine an appropriate course of action. The evaluation would include additional monitoring, source identification, implementation of interim protective measures (if necessary), and delineation of extent. These evaluations are necessary to determine an appropriate response action for the Ogallala. The primary goal of the Plan is to provide for the continued protection of the Ogallala Aquifer and the health of its consumers. In recognition, this Plan presents a flexible and rational approach for making future decisions associated with confirming the change in perched and Ogallala aquifer conditions and identifying a response (technical activities, changes to response actions, regulatory oversight, and public involvement).

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

The QuakeSim Project: Numerical Simulations for Active Tectonic Processes

In order to develop a solid earth science framework for understanding and studying of active tectonic and earthquake processes, this task develops simulation and analysis tools to study the physics of earthquakes using state-of-the art modeling, data manipulation, and pattern recognition technologies. We develop clearly defined accessible data formats and code protocols as inputs to the simulations. these are adapted to high-performance computers because the solid earth system is extremely complex and nonlinear resulting in computationally intensive problems with millions of unknowns. With these tools it will be possible to construct the more complex models and simulations necessary to develop hazard assessment systems critical for reducing future losses from major earthquakes.

tectonic processes↗

Discovery of a Plains Caldera Complex and Extinct Lava Lake in Arabia Terra, Mars: Implications for the Discovery of Additional Highland Volcanic Source Regions

Several irregularly shaped topographic depressions occur near the dichotomy boundary in northern Arabia Terra, Mars. The geomorphology of these features suggests that they formed by collapse, opposed to meteor impact. At least one depression (approx.55 by 85 km) displays geologic features indicating a complex, multi-stage collapse history. Features within and around the collapse structure indicate volcanic processes. The complex occurs within Hesperian ridged plains of likely volcanic origin and displays no crater rim or evidence for ejecta. Instead the depression consists of a series of circumferential graben and down-dropped blocks which also display upper surfaces similar to ridged plain lavas. Large blocks within the depression are tilted towards the crater center, and display graben that appear to have originally been linked with circumferential graben outside of the complex related to earlier collapse events. A nearly 700 m high mound exists along a graben within the complex that might be a vent. The deepest depression displays two sets of nearly continuous terraces, which we interpret as high-stands of a drained lava lake. These features appear similar to the black ledge described during the Kilauea Iki eruption in 1959. A lacustrine origin for the terraces seems unlikely because of the paucity of channels found in or around the depression that could be linked to aqueous surface processes. In addition, there is no obvious evidence for lacustrine sediments within the basin. Together with the presence of significant faulting that is indicative of collapse we conclude that this crater complex represents a large caldera formed in the Late Noachian to Early Hesperian. Other linear and irregular depressions in the region also might be linked to ancient volcanism. If that hypothesis is correct, it suggests that northern Arabia Terra could contain a large, previously unrecognized highland igneous province. Evacuation of magma via explosive and effusive activity produced localized collapse, might have contributed to nearby ridged plains, and pyroclastic materials erupted from these vents might have supplied sediments in fretted terrain and other deposits. The recognition of volcanoes within Arabia Terra expands the known extent of Noachian-Hesperian volcanism to cover much of the preserved martian highland crust.

Bleacher, Jacob↗

Fyn–Saracatinib Complex Structure Reveals an Active State-like Conformation

Fyn is a Src-family tyrosine kinase implicated in synaptic dysfunction and neuroinflammation across multiple neurodegenerative disorders, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Saracatinib (AZD0530) is a potent Src-family inhibitor that has been explored as a repurposed therapeutic; however, its clinical utility is limited by poor kinase selectivity caused by high sequence conservation within Src-family ATP-binding sites. Here, we combine surface plasmon resonance (SPR) and X-ray crystallography to define saracatinib recognition by the Fyn kinase domain (KD). SPR single-cycle kinetics shows that saracatinib binds the isolated Fyn KD and full-length Fyn with low-nanomolar affinity, whereas dasatinib binds with subnanomolar affinity and markedly slower dissociation. We determined the crystal structure of the Fyn KD-saracatinib complex at 2.22 Å resolution. The kinase adopts an active-like conformation with the DFG motif and αC-helix in the ‘in’ state and a conserved β3 αC Lys-Glu salt bridge. Saracatinib occupies the adenine and ribose pockets, and engages the hinge through direct and water-mediated hydrogen bonding while complementing a hydrophobic back pocket by van der Waals contacts. Comparison with reported saracatinib-bound structures of other kinases suggests that the active-state geometry observed for Fyn creates a pocket not observed in inactive-like complexes, providing a structural handle for designing Fyn-selective inhibitors. Comparison with all saracatinib-bound kinase co-structures currently available in the PDB (ALK2 and PKMYT1) indicates a conserved monodentate hinge binding mode but kinase-dependent αC-helix conformations, providing a structural rationale for designing Fyn-selective analogues.

AZD0530↗

Architecting Ourselves: Schema to Facilitate Growth of the International Space Architecture Community

This paper develops a conceptual model, adapted from the way research and development non-profits and universities tend to be organized, that could help amplify the reach and effectiveness of the international space architecture community. The model accommodates current activities and published positions, and increases involvement by allocating accountability for necessary professional and administrative activities. It coordinates messaging and other outreach functions to improve brand management. It increases sustainability by balancing volunteer workload. And it provides an open-ended structure that can be modified gracefully as needs, focus, and context evolve. Over the past 20 years, Space Architecture has attained some early signs of legitimacy as a discipline: an active, global community of practicing and publishing professionals; university degree programs; a draft undergraduate curriculum; and formal committee establishment within multiple professional organizations. However, the nascent field has few outlets for expression in built architecture, which exacerbates other challenges the field is experiencing in adolescence: obtaining recognition and inclusion as a unique contributor by the established aerospace profession; organizing and managing outreach by volunteers; striking a balance between setting admittance or performance credentials and attaining a critical mass of members; and knowing what to do, beyond sharing common interests, to actually increase the market demand for space architecture. This paper develops a conceptual model, adapted from the way research-anddevelopment non-profits and universities tend to be organized, that could help amplify the reach and effectiveness of the international space architecture community. The model accommodates current activities and published positions, and increases involvement by allocating accountability for necessary professional and administrative activities. It coordinates messaging and other outreach functions to improve brand management. It increases sustainability by balancing volunteer workload. And it provides an open-ended structure that can be modified gracefully as needs, focus, and context evolve. This organizational model is offered up for consideration, debate, and toughening by the space architecture community at large.

space architecure↗

Fuzzy set methods for object recognition in space applications

Progress on the following tasks is reported: feature calculation; membership calculation; clustering methods (including initial experiments on pose estimation); and acquisition of images (including camera calibration information for digitization of model). The report consists of 'stand alone' sections, describing the activities in each task. We would like to highlight the fact that during this quarter, we believe that we have made a major breakthrough in the area of fuzzy clustering. We have discovered a method to remove the probabilistic constraints that the sum of the memberships across all classes must add up to 1 (as in the fuzzy c-means). A paper, describing this approach, is included.

Keller, James M.↗