Objectives and Progress on Ground Vibration Testing for the Ares Launch Vehicles

NASA has conducted dynamic tests on each of its major launch vehicles during the past 45 years. Each test has provided invaluable data to correlate and correct analytical models used to predict structural responses to differing dynamics for these vehicles. With both Saturn V and Space Shuttle, hardware changes were also required to the flight vehicles to ensure crew and vehicle safety. The Ares I IVGVT will undoubtedly provide similar valuable test data to support successful flights of the Constellation Program. The IVGVT will provide test determined natural frequencies, mode shapes and damping for the Ares I. This data will be used to support controls analysis by providing this test data to reduce uncertainty in the models. The value of this testing has been proven by past launch vehicle successes and failures. Performing dynamic testing on the Ares vehicles will provide confidence that the launch vehicles will be safe and successful in their missions. In addition, IVGVT will provide the following benefits for the Ares rockets: a) IVGVT data along with Ares development flights like Ares I-X, Ares I-Y, Ares I-X Prime, and Orion-1 or others will reduce the risk to the Orion-2 crew. IVGVT will permit anchoring the various analytical and operational models used in so many different aspects of Ares operations. b) IVGVT data will permit better understanding of the structural and GN&C margins of the spacecraft and may permit mass savings or expanded day-of-launch opportunities or fewer constraints to launch. c) Undoubtedly IVGVT will uncover some of the "unknown unknowns" so often seen in developing, launching, and flying new spacecraft vehicles and data from IVGVT may help prevent a loss of vehicle or crew. d) IVGVT also will be the first time Ares I flight-like hardware is transported, handled, rotated, mated, stacked, and integrated. e) Furthermore, handling and stacking the IVGVT launch vehicle stacks will be an opportunity to understand certain aspects of vehicle operability much better (for example, handling procedures, touch-labor time to accomplish tasks, access at interfaces, access to stage mating bolts, access to avionics boxes, access to the Interstage, GSE functionality, and many other important aspects of Ares I operability). All of these results will provide for better vehicle safety and better stewardship of national resources as NASA begins its next phase of human space exploration

Serial MR diffusion to predict treatment response in high-grade pediatric brain tumors: a comparison of regional and voxel-based diffusion change metrics

Background Assessment of treatment response by measuring tumor size is known to be a late and potentially confounded response index. Serial diffusion MRI has shown potential for allowing earlier and possibly more reliable response assessment in adult patients, with limited experience in clinical settings and in pediatric brain cancer. We present a retrospective study of clinical MRI data in children with high-grade brain tumors to assess and compare the values of several diffusion change metrics to predict treatment response. Methods Eighteen patients (age range, 1.9–20.6 years) with high-grade brain tumors and serial diffusion MRI (pre- and posttreatment interval range, 1–16 weeks posttreatment) were identified after obtaining parental consent. The following diffusion change metrics were compared with the clinical response status assessed at 6 months: (1) regional change in absolute and normalized apparent diffusivity coefficient (ADC), (2) voxel-based fractional volume of increased (fiADC) and decreased ADC (fdADC), and (3) a new metric based on the slope of the first principal component of functional diffusion maps (fDM). Results Responders (n = 12) differed significantly from nonresponders (n = 6) in all 3 diffusional change metrics demonstrating higher regional ADC increase, larger fiADC, and steeper slopes (P < .05). The slope method allowed the best response prediction (P < .01, η2 = 0.78) with a classification accuracy of 83% for a slope of 58° using receiver operating characteristic (ROC) analysis. Conclusions We demonstrate that diffusion change metrics are suitable response predictors for high-grade pediatric tumors, even in the presence of variable clinical diffusion imaging protocols

Sex Ratio Variation between Ejaculates Within Sire Evaluated by Polymerase Chain Reaction, Calving, and Farrowing Records

Ejaculates from sires were examined by polymerase chain reaction to determine percentage of sperm bearing the Y chromosome. Results were verified by examining the percentage of male calves per ejaculate used in artificial insemination (AI) and the percentage of male piglets per litter from a controlled mating program. Spermatozoal DNA was amplified by polymerase chain reaction with specific primers for the Y chromosome. Image analysis measured the fluorescent intensity of the 194-bp band. Ejaculates were compared with a pooled standard of spermatozoal DNA equated to a 50% Y-bearing sperm ejaculate. Calving data were obtained from information collected for the National Association of Animal Breeders for dystocia evaluation of cows bred to AI bulls. Breeding data were obtained from AI technician receipts. Calving and breeding data were merged on cow, sire, calving date, and breeding date. The percentage of males was calculated per sire, ejaculate, and herd combination. Farrowing data were evaluated for the percentage of male piglets per litter. Ejaculates within bulls contributed to variation (24 ± 9.8% to 84 ± 9.8%) in the percentage of sperm bearing the Y chromosome. Ejaculates from the same bull contributed to variation in the percentage of male calves (16.1 to 72.3%). Ejaculates from the same boar contributed to variation in the percentage of male piglets that ranged from 7.8 to 94.7%. These percentages and the results obtained by polymerase chain reaction analysis of ejaculates suggested that spermatozoa bearing X and Y chromosomes were unequally represented in ejaculates. The use of ejaculates screened by polymerase chain reaction could enhance production of the desired sex of calf

Imaging biomarker roadmap for cancer studies.

Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing 'translational gaps' through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored 'roadmap'. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use.Development of this roadmap received support from Cancer Research UK and the Engineering and Physical Sciences Research Council (grant references A/15267, A/16463, A/16464, A/16465, A/16466 and A/18097), the EORTC Cancer Research Fund, and the Innovative Medicines Initiative Joint Undertaking (grant agreement number 115151), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies' in kind contribution

Contrast-enhanced MR angiography

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42396/1/261-23-5-469_23n5p469.pd

Three-dimensional static displacement, stimulated echo NMR elasticity imaging

This article presents a method for measuring three-dimensional mechanical displacement and strain fields using stimulated echo MRI. Additional gradient pulses encode internal displacements in response to an externally applied deformation. By limiting the mechanical transition to the stimulated echo mixing time, a more accurate static displacement measurement is obtained. A three-dimensional elasticity reconstruction within a region of interest having a uniform shear modulus along its boundary is performed by numerically solving discretized elasticity equilibrium equations. Data acquisition, strain measurements and reconstruction were performed using a silicone gel phantom containing an inclusion of known elastic properties. A comparison between two-dimensional and three-dimensional reconstructions from simulated and experimental displacement data shows higher accuracy from the three-dimensional reconstruction. The long-term objective of this work is to provide a method for remotely palpating and elastically quantitating manually inaccessible tissues.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48966/2/m00616.pd

Comparative Live-Cell Imaging Analyses of SPA-2, BUD-6 and BNI-1 in Neurospora crassa Reveal Novel Features of the Filamentous Fungal Polarisome

A key multiprotein complex involved in regulating the actin cytoskeleton and secretory machinery required for polarized growth in fungi, is the polarisome. Recognized core constituents in budding yeast are the proteins Spa2, Pea2, Aip3/Bud6, and the key effector Bni1. Multicellular fungi display a more complex polarized morphogenesis than yeasts, suggesting that the filamentous fungal polarisome might fulfill additional functions. In this study, we compared the subcellular organization and dynamics of the putative polarisome components BUD-6 and BNI-1 with those of the bona fide polarisome marker SPA-2 at various developmental stages of Neurospora crassa. All three proteins exhibited a yeast-like polarisome configuration during polarized germ tube growth, cell fusion, septal pore plugging and tip repolarization. However, the localization patterns of all three proteins showed spatiotemporally distinct characteristics during the establishment of new polar axes, septum formation and cytokinesis, and maintained hyphal tip growth. Most notably, in vegetative hyphal tips BUD-6 accumulated as a subapical cloud excluded from the Spitzenkörper (Spk), whereas BNI-1 and SPA-2 partially colocalized with the Spk and the tip apex. Novel roles during septal plugging and cytokinesis, connected to the reinitiation of tip growth upon physical injury and conidial maturation, were identified for BUD-6 and BNI-1, respectively. Phenotypic analyses of gene deletion mutants revealed additional functions for BUD-6 and BNI-1 in cell fusion regulation, and the maintenance of Spk integrity. Considered together, our findings reveal novel polarisome-independent functions of BUD-6 and BNI-1 in Neurospora, but also suggest that all three proteins cooperate at plugged septal pores, and their complex arrangement within the apical dome of mature hypha might represent a novel aspect of filamentous fungal polarisome architecture

Intravoxel water diffusion heterogeneity imaging of human high-grade gliomas

This study aimed to determine the potential value of intravoxel water diffusion heterogeneity imaging for brain tumor characterization and evaluation of high-grade gliomas, by comparing an established heterogeneity index ( Α value) measured in human high-grade gliomas to those of normal appearing white and grey matter landmarks. Twenty patients with high-grade gliomas prospectively underwent diffusion-weighted magnetic resonance imaging using multiple b-values. The stretched-exponential model was used to generate Α and distributed diffusion coefficient (DDC) maps. The Α values and DDCs of the tumor and contralateral anatomic landmarks were measured in each patient. Differences between Α values of tumors and landmark tissues were assessed using paired t- tests. Correlation between tumor Α and tumor DDC was assessed using Pearson's correlation coefficient. Mean Α of tumors was significantly lower than that of contralateral frontal white matter ( p  = 0.0249), basal ganglia ( p  < 0.0001), cortical grey matter ( p  < 0.0001), and centrum semiovale ( p  = 0.0497). Correlation between tumor Α and tumor DDC was strongly negative (Pearson correlation coefficient, −0.8493; p  < 0.0001). The heterogeneity index Α of human high-grade gliomas is significantly different from those of normal brain structures, which potentially offers a new method for evaluating brain tumors. The observed negative correlation between tumor Α and tumor DDC requires further investigation. Copyright © 2009 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65045/1/1441_ftp.pd

DW-MRI as a Biomarker to Compare Therapeutic Outcomes in Radiotherapy Regimens Incorporating Temozolomide or Gemcitabine in Glioblastoma

The effectiveness of the radiosensitizer gemcitabine (GEM) was evaluated in a mouse glioma along with the imaging biomarker diffusion-weighted magnetic resonance imaging (DW-MRI) for early detection of treatment effects. A genetically engineered murine GBM model [Ink4a-Arf−/− PtenloxP/loxP/Ntv-a RCAS/PDGF(+)/Cre(+)] was treated with gemcitabine (GEM), temozolomide (TMZ) +/− ionizing radiation (IR). Therapeutic efficacy was quantified by contrast-enhanced MRI and DW-MRI for growth rate and tumor cellularity, respectively. Mice treated with GEM, TMZ and radiation showed a significant reduction in growth rates as early as three days post-treatment initiation. Both combination treatments (GEM/IR and TMZ/IR) resulted in improved survival over single therapies. Tumor diffusion values increased prior to detectable changes in tumor volume growth rates following administration of therapies. Concomitant GEM/IR and TMZ/IR was active and well tolerated in this GBM model and similarly prolonged median survival of tumor bearing mice. DW-MRI provided early changes to radiosensitization treatment warranting evaluation of this imaging biomarker in clinical trials