Biplane Fluoroscopy for Hindfoot Motion Analysis during Gait: A Model-based Evaluation

The purpose of this study was to quantify the accuracy and precision of a biplane fluoroscopy system for model-based tracking of in vivo hindfoot motion during over-ground gait. Gait was simulated by manually manipulating a cadaver foot specimen through a biplane fluoroscopy system attached to a walkway. Three 1.6-mm diameter steel beads were implanted into the specimen to provide marker-based tracking measurements for comparison to model-based tracking. A CT scan was acquired to define a gold standard of implanted bead positions and to create 3D models for model-based tracking. Static and dynamic trials manipulating the specimen through the capture volume were performed. Marker-based tracking error was calculated relative to the gold standard implanted bead positions. The bias, precision, and root-mean-squared (RMS) error of model-based tracking was calculated relative to the marker-based measurements. The overall RMS error of the model-based tracking method averaged 0.43 ± 0.22 mm and 0.66 ± 0.43° for static and 0.59 ± 0.10 mm and 0.71 ± 0.12° for dynamic trials. The model-based tracking approach represents a non-invasive technique for accurately measuring dynamic hindfoot joint motion during in vivo, weight bearing conditions. The model-based tracking method is recommended for application on the basis of the study results

ADP release is the rate-limiting step of the MT activated ATPase of non-claret disjunctional and kinesin

AbstractThe motor protein non-claret disjunctional (ncd) moves towards the minus ends of microtubules (MTs), whereas its close relative kinesin moves in the opposite direction towards the plus ends of MTs. The mechanisms of movement and directional reversal for these motor proteins are unknown. Here we report the rate constants for MT activated ADP release from a recombinant double-headed ncd protein, GST-MC5, and a recombinant double-headed kinesin protein, KΔ401, measured using the fluorescent nucleotide analogues methylanthranilyol ATP (mantATP) and mantADP. Comparison of the maximal MT activated mantADP release rates for these proteins with their maximal MT activated mantATP turnover rates indicates that ADP release is the rate-limiting step for ATP turnover for both ncd and kinesin. This data supports the view that directional reversal may result from structural rather than chemical kinetic differences in the way the motors interact with MTs

Systematic derivation of a rotationally covariant extension of the 2-dimensional Newell-Whitehead-Segel equation

An extension of the Newell-Whitehead-Segel amplitude equation covariant under abritrary rotations is derived systematically by the renormalization group method.Comment: 8 pages, to appear in Phys. Rev. Letters, March 18, 199

"Making Safety Happen" Through Probabilistic Risk Assessment at NASA

NASA is using Probabilistic Risk Assessment (PRA) as one of the tools in its Safety & Mission Assurance (S&MA) tool belt to identify and quantify risks associated with human spaceflight. This paper discusses some of the challenges and benefits associated with developing and using PRA for NASA human space programs. Some programs have entered operation prior to developing a PRA, while some have implemented PRA from the start of the program. It has been observed that the earlier a design change is made in the concept or design phase, the less impact it has on cost and schedule. Not finding risks until the operation phase yields much costlier design changes and major delays, which can result in discussions of just accepting the risk. Risk contributors identified by PRA are not just associated with hardware failures. They include but are not limited to crew fatality due to medical causes, the environment the vehicle and crew are exposed to, the software being used, and the reliability of the crew performing required actions. Some programs have entered operation prior to developing a PRA, and while PRA can still provide a benefit for operations and future design trades, the benefit of implementing PRA from the start of the program provides the added benefit of informing design and reducing risk early in program development. Currently, NASAs International Space Station (ISS) program is in its 20th year of on-orbit operations around the Earth and has several new programs in the design phase preparing to enter the operation phase all of which have active (or living) PRAs. These programs incorporate PRA as part of their Risk-Informed, Decision-Making (RIDM) process. For new NASA human spaceflight programs discussion begins with mission concept, establishing requirements, forming the PRA team, and continues through the design cycles into the operational phase. Several examples of PRA related applications and observed lessons are included

The VISTA Science Archive

We describe the VISTA Science Archive (VSA) and its first public release of data from five of the six VISTA Public Surveys. The VSA exists to support the VISTA Surveys through their lifecycle: the VISTA Public Survey consortia can use it during their quality control assessment of survey data products before submission to the ESO Science Archive Facility (ESO SAF); it supports their exploitation of survey data prior to its publication through the ESO SAF; and, subsequently, it provides the wider community with survey science exploitation tools that complement the data product repository functionality of the ESO SAF. This paper has been written in conjunction with the first public release of public survey data through the VSA and is designed to help its users understand the data products available and how the functionality of the VSA supports their varied science goals. We describe the design of the database and outline the database-driven curation processes that take data from nightly pipeline-processed and calibrated FITS files to create science-ready survey datasets. Much of this design, and the codebase implementing it, derives from our earlier WFCAM Science Archive (WSA), so this paper concentrates on the VISTA-specific aspects and on improvements made to the system in the light of experience gained in operating the WSA.Comment: 22 pages, 16 figures. Minor edits to fonts and typos after sub-editting. Published in A&

Ares I-X First Flight Loss of Vehicle Probability Analysis

As part of the Constellation (Cx) Program development effort, several test flights were planned to prove concepts and operational capabilities of the new vehicles being developed. The first test, involving the Eastern Test Range, is the Ares I-X launched in 2009. As part of this test, the risk to the general public was addressed to ensure it is within Air Force requirements. This paper describes the methodology used to develop first flight estimates of overall loss of vehicle (LOV) failure probability, specifically for the Ares I-X. The method described in this report starts with the Air Force s generic failure probability estimate for first flight and adjusts the value based on the complexity of the vehicle as compared to the complexity of a generic vehicle. The results estimate a 1 in 9 probability of failure. The paper also describes traditional PRA methods used in this assessment, which were then combined with the updated first flight risk methodology to generate inputs required by the malfunction turn analysis to support estimate of casualty (Ec) calculations as part of the Final Flight Data Package (FFDP) delivered to the Eastern Range for Final Flight Plan Approval

Taxol acts differently on different tubulin isotypes

Taxol is a small molecule effector that allosterically locks tubulin into the microtubule lattice. We show here that taxol has different effects on different single-isotype microtubule lattices. Using in vitro reconstitution, we demonstrate that single-isotype α1β4 GDP-tubulin lattices are stabilised and expanded by 10 μM taxol, as reported by accelerated microtubule gliding in kinesin motility assays, whereas single-isotype α1β3 GDP-tubulin lattices are stabilised but not expanded. This isotype-specific action of taxol drives gliding of segmented-isotype GDP-taxol microtubules along convoluted, sinusoidal paths, because their expanded α1β4 segments try to glide faster than their compacted α1β3 segments. In GMPCPP, single-isotype α1β3 and α1β4 lattices both show accelerated gliding, indicating that both can in principle be driven to expand. We therefore propose that taxol-induced lattice expansion requires a higher taxol occupancy than taxol-induced stabilisation, and that higher taxol occupancies are accessible to α1β4 but not α1β3 single-isotype lattices

In vivo evolution of biopsy-proven inflammatory demyelination quantified by R2t* mapping

A 35-year-old man with an enhancing tumefactive brain lesion underwent biopsy, revealing inflammatory demyelination. We used quantitative Gradient-Recalled-Echo (qGRE) MRI to visualize and measure tissue damage in the lesion. Two weeks after biopsy, qGRE showed significant R2t* reduction in the left optic radiation and surrounding tissue, consistent with the histopathological and clinical findings. qGRE was repeated 6 and 14 months later, demonstrating partially recovered optic radiation R2t*, in concert with improvement of the hemianopia to ultimately involve only the lower right visual quadrant. These results support qGRE metrics as in vivo biomarkers for tissue damage and longitudinal monitoring of demyelinating disease

Backstepping mechanism of kinesin-1

Kinesin-1 is an ATP-driven molecular motor that transports cellular cargo along microtubules. At low loads, kinesin-1 almost always steps forward, toward microtubule plus ends, but at higher loads, it can also step backward. Backsteps are usually 8 nm but can be larger. These larger backward events of 16 nm, 24 nm, or more are thought to be slips rather than steps because they are too fast to consist of multiple, tightly coupled 8-nm steps. Here, we propose that not only these larger backsteps, but all kinesin-1 backsteps, are slips. We show first that kinesin waits before forward steps for less time than before backsteps and detachments; second, we show that kinesin waits for the same amount of time before backsteps and detachments; and third, we show that by varying the microtubule type, we can change the ratio of backsteps to detachments without affecting forward stepping. Our findings indicate that backsteps and detachments originate from the same state and that this state arises later in the mechanochemical cycle than the state that gives rise to forward steps. To explain our data, we propose that, in each cycle of ATP turnover, forward kinesin steps can only occur before Pi release, whereas backslips and detachments can only occur after Pi release. In the scheme we propose, Pi release gates access to a weak binding K⋅ADP-K⋅ADP state that can slip back along the microtubule, re-engage, release ADP, and try again to take an ATP-driven forward step. We predict that this rescued detachment pathway is key to maintaining kinesin processivity under load

Evaluating brain damage in multiple sclerosis with simultaneous multi-angular-relaxometry of tissue

OBJECTIVE: Multiple sclerosis (MS) is a common demyelinating central nervous system disease. MRI methods that can quantify myelin loss are needed for trials of putative remyelinating agents. Quantitative magnetization transfer MRI introduced the macromolecule proton fraction (MPF), which correlates with myelin concentration. We developed an alternative approach, Simultaneous-Multi-Angular-Relaxometry-of-Tissue (SMART) MRI, to generate MPF. Our objective was to test SMART-derived MPF metric as a potential imaging biomarker of demyelination. METHODS: Twenty healthy control (HC), 11 relapsing-remitting MS (RRMS), 22 progressive MS (PMS), and one subject with a biopsied tumefactive demyelinating lesion were scanned at 3T using SMART MRI. SMART-derived MPF metric was determined in normal-appearing cortical gray matter (NAGM), normal-appearing subcortical white matter (NAWM), and demyelinating lesions. MPF metric was evaluated for correlations with physical and cognitive test scores. Comparisons were made between HC and MS and between MS subtypes. Furthermore, correlations were determined between MPF and neuropathology in the biopsied person. RESULTS: SMART-derived MPF in NAGM and NAWM were lower in MS than HC (p \u3c 0.001). MPF in NAGM, NAWM and lesions differentiated RRMS from PMS (p \u3c 0.01, p \u3c 0.001, p \u3c 0.001, respectively), whereas lesion volumes did not. MPF in NAGM, NAWM and lesions correlated with the Expanded Disability Status Scale (p \u3c 0.01, p \u3c 0.001, p \u3c 0.001, respectively) and nine-hole peg test (p \u3c 0.001, p \u3c 0.001, p \u3c 0.01, respectively). MPF was lower in the histopathologically confirmed inflammatory demyelinating lesion than the contralateral NAWM and increased in the biopsied lesion over time, mirroring improved clinical performance. INTERPRETATION: SMART-derived MPF metric holds potential as a quantitative imaging biomarker of demyelination and remyelination