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Several researchers have recently discussed problems with Superpave volumetric mix design. Anderson and Bahia believe that evaluating and selecting the aggregate gradation to achieve minimum voids in the mineral aggregate (VMA) is the most difficult and time-consuming step in the mix design process (1). Hinrichsen and Heggen feel that the minimum VMA requirement

The Octarepeat Domain of the Prion Protein Binds Cu(II) with Three Distinct Coordination Modes at pH 7.4

The prion protein (PrP) binds Cu2+ in its N-terminal octarepeat domain. This unusual domain is comprised of four or more tandem repeats of the fundamental sequence PHGGGWGQ. Previous work from our laboratories demonstrates that at full copper occupancy, each HGGGW segment binds a single Cu2+. However, several recent studies suggest that low copper occupancy favors different coordination modes, possibly involving imidazoles from histidines in adjacent octapeptide segments. This is investigated here using a combination of X-band EPR, S-band EPR, and ESEEM, along with a library of modified peptides designed to favor different coordination interactions. At pH 7.4, three distinct coordination modes are identified. Each mode is fully characterized to reveal a series of copper-dependent octarepeat domain structures. Multiple His coordination is clearly identified at low copper stoichiometry. In addition, EPR detected copper−copper interactions at full occupancy suggest that the octarepeat domain partially collapses, perhaps stabilizing this specific binding mode and facilitating cooperative copper uptake. This work provides the first complete characterization of all dominant copper coordination modes at pH 7.4

Error Propagation Analysis in the SAE Architecture Analysis and Design Language (AADL) and the EDICT Tool Framework

This report documents the capabilities of the EDICT tools for error modeling and error propagation analysis when operating with models defined in the Architecture Analysis & Design Language (AADL). We discuss our experience using the EDICT error analysis capabilities on a model of the Scalable Processor-Independent Design for Enhanced Reliability (SPIDER) architecture that uses the Reliable Optical Bus (ROBUS). Based on these experiences we draw some initial conclusions about model based design techniques for error modeling and analysis of highly reliable computing architectures

The Flattened Dark Halo of Polar Ring Galaxy NGC 4650A: A Conspiracy of Shapes?

Kinematics and photometry of the polar ring galaxy NGC 4650A, including new observations of the rotation and velocity dispersion of its central stellar disk, are used to infer the presence of a dark matter halo and to measure its shape. Fits to the observed disk and polar ring rotation curves from detailed mass and photometric modeling rule out a spherical dark halo. The best fit models have halos with isodensity surfaces that are flattened to a shape between E6 and E7 (axis ratios between 0.4 and 0.3); the asymptotic equatorial speeds of these models are in excellent agreement with the I-band Tully-Fisher relation. This degree of dark halo flattening is larger than that expected from N-body collapse simulations of dissipationless dark matter. Since the kinematics and surface brightness profile of the central luminous body indicate that its light has an intrinsic axis ratio c/a \lsim 0.4, in NGC 4650A the radial ``conspiracy" between the dark and luminous components that leads to flat rotation curves may extend to the {\it shape} of the mass distribution as well.Comment: Uuencoded compressed tar file (complete with figures). Institute for Advanced Study number AST 94/2

The diagnostic performance of CA125 for the detection of ovarian and non-ovarian cancer in primary care: a population-based cohort study

Background The serum biomarker Cancer Antigen 125 (CA125) is widely used as an investigation for possible ovarian cancer in symptomatic women presenting to primary care. However, its diagnostic performance in this setting is unknown. We evaluated the performance of CA125 in primary care for the detection of ovarian and non-ovarian cancers. Methods and findings We studied women in the UK Clinical Practice Research Datalink with a CA125 test performed between 1 May 2011 – 31 December 2014. Ovarian and non-ovarian cancers diagnosed in the year following CA125 testing were identified from the cancer registry. Women were categorised by age: <50 years and ≥50 years. Conventional measures of test diagnostic accuracy, including sensitivity, specificity and positive predictive value, were calculated for the standard CA125 cut-off (≥35 U/ml). The probability of a woman having cancer at each CA125 level between 1-1000 U/ml was estimated using logistic regression. Cancer probability was also estimated on the basis of CA125 level and age in years using logistic regression. We identified CA125 levels equating to a 3% estimated cancer probability: the ‘risk threshold’ at which the UK National Institute for Health and Care Excellence advocates urgent specialist cancer investigation. 50,780 women underwent CA125 testing; 456 (0.9%) were diagnosed with ovarian cancer and 1321 (2.6%) with non-ovarian cancer. 3.4% of women <50 years and 15.2% of women ≥50 years with CA125 levels ≥35 U/ml, had ovarian cancer. 20.4% of women ≥50 years with a CA125 level ≥35 U/ml, who did not have ovarian cancer, were diagnosed with a non-ovarian cancer. A CA125 value of 53 U/ml equated to a 3% probability of ovarian cancer overall. This varied by age, with a value of 104 U/ml in 40-year-old women and 32 U/ml in 70-year-old women, equating to a 3% probability. The main limitations of our study were that we were unable to determine why CA125 tests were performed and that our findings are based solely on UK primary care data, so caution is need in extrapolating them to other healthcare settings. Conclusions CA125 is a useful test for ovarian cancer detection in primary care, particularly in women ≥50 years old. Clinicians should also consider non-ovarian cancers in women with high CA125 levels, especially if ovarian cancer has been excluded, in order to prevent diagnostic delay. Our results enable clinicians and patients to determine the estimated probability of ovarian cancer and all cancers at any CA125 level and age, which can be used to guide individual decisions on the need for further investigation or referral.National Institute of Health Research (NIHR) School of Primary Care Research [FR17 424]. Cancer Research UK [C8640/A23385]

Insights into the Control of Drug Release from Complex Immediate Release Formulations.

The kinetics of water transport into tablets, and how it can be controlled by the formulation as well as the tablet microstructure, are of central importance in order to design and control the dissolution and drug release process, especially for immediate release tablets. This research employed terahertz pulsed imaging to measure the process of water penetrating through tablets using a flow cell. Tablets were prepared over a range of porosity between 10% to 20%. The formulations consist of two drugs (MK-8408: ruzasvir as a spray dried intermediate, and MK-3682: uprifosbuvir as a crystalline drug substance) and NaCl (0% to 20%) at varying levels of concentrations as well as other excipients. A power-law model is found to fit the liquid penetration exceptionally well (average R2>0.995). For each formulation, the rate of water penetration, extent of swelling and the USP dissolution rate were compared. A factorial analysis then revealed that the tablet porosity was the dominating factor for both liquid penetration and dissolution. NaCl more significantly influenced liquid penetration due to osmotic driving force as well as gelling suppression, but there appears to be little difference when NaCl loading in the formulation increases from 5% to 10%. The level of spray dried intermediate was observed to further limit the release of API in dissolution

The Influence of Motion and Stress on Optical Fibers

We report on extensive testing carried out on the optical fibers for the VIRUS instrument. The primary result of this work explores how 10+ years of simulated wear on a VIRUS fiber bundle affects both transmission and focal ratio degradation (FRD) of the optical fibers. During the accelerated lifetime tests we continuously monitored the fibers for signs of FRD. We find that transient FRD events were common during the portions of the tests when motion was at telescope slew rates, but dropped to negligible levels during rates of motion typical for science observation. Tests of fiber transmission and FRD conducted both before and after the lifetime tests reveal that while transmission values do not change over the 10+ years of simulated wear, a clear increase in FRD is seen in all 18 fibers tested. This increase in FRD is likely due to microfractures that develop over time from repeated flexure of the fiber bundle, and stands in contrast to the transient FRD events that stem from localized stress and subsequent modal diffusion of light within the fibers. There was no measurable wavelength dependence on the increase in FRD over 350 nm to 600 nm. We also report on bend radius tests conducted on individual fibers and find the 266 microns VIRUS fibers to be immune to bending-induced FRD at bend radii of R > 10cm. Below this bend radius FRD increases slightly with decreasing radius. Lastly, we give details of a degradation seen in the fiber bundle currently deployed on the Mitchell Spectrograph (formally VIRUS-P) at McDonald Observatory. The degradation is shown to be caused by a localized shear in a select number of optical fibers that leads to an explosive form of FRD. In a few fibers, the overall transmission loss through the instrument can exceed 80%.Comment: 19 pages, 22 figure

PKS 1830-211: A Face-On Spiral Galaxy Lens

We present new Hubble Space Telescope images of the gravitational lens PKS 1830-211, which allow us to characterize the lens galaxy and update the determination of the Hubble constant from this system. The I-band image shows that the lens galaxy is a face-on spiral galaxy with clearly delineated spiral arms. The southwestern image of the background quasar passes through one of the spiral arms, explaining the previous detections of large quantities of molecular gas and dust in front of this image. The lens galaxy photometry is consistent with the Tully-Fisher relation, suggesting the lens galaxy is a typical spiral galaxy for its redshift. The lens galaxy position, which was the main source of uncertainty in previous attempts to determine H_0, is now known precisely. Given the current time delay measurement and assuming the lens galaxy has an isothermal mass distribution, we compute H_0 = 44 +/- 9 km/s/Mpc for an Omega_m = 0.3 flat cosmological model. We describe some possible systematic errors and how to reduce them. We also discuss the possibility raised by Courbin et al. (2002), that what we have identified as a single lens galaxy is actually a foreground star and two separate galaxies.Comment: 21 pp., 4 figs., accepted by ApJ, section added to discuss related work by Courbin et al. (astro-ph/0202026