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A novel Gerstmann-Str\ue4ussler-Scheinker disease mutation defines a precursor for amyloidogenic 8 kDa PrP fragments and reveals N-terminal structural changes shared by other GSS alleles
No full textTo explore pathogenesis in a young Gerstmann-Str\ue4ussler-Scheinker Disease (GSS) patient, the corresponding mutation, an eight-residue duplication in the hydrophobic region (HR), was inserted into the wild type mouse PrP gene. Transgenic (Tg) mouse lines expressing this mutation (Tg.HRdup) developed spontaneous neurologic syndromes and brain extracts hastened disease in low-expressor Tg.HRdup mice, suggesting de novo formation of prions. While Tg.HRdup mice exhibited spongiform change, PrP aggregates and the anticipated GSS hallmark of a proteinase K (PK)-resistant 8 kDa fragment deriving from the center of PrP, the LGGLGGYV insertion also imparted alterations in PrP's unstructured N-terminus, resulting in a 16 kDa species following thermolysin exposure. This species comprises a plausible precursor to the 8 kDa PK-resistant fragment and its detection in adolescent Tg.HRdup mice suggests that an early start to accumulation could account for early disease of the index case. A 16 kDa thermolysin-resistant signature was also found in GSS patients with P102L, A117V, H187R and F198S alleles and has coordinates similar to GSS stop codon mutations. Our data suggest a novel shared pathway of GSS pathogenesis that is fundamentally distinct from that producing structural alterations in the C-terminus of PrP, as observed in other prion diseases such as Creutzfeldt-Jakob Disease and scrapie.Peer reviewed: YesNRC publication: Ye
A-type stellar abundances: a corollary to Herschel observations of debris disks
No full textIn order to assess the relationship between metallicity and exoplanetary systems, we compare the abundances of AF-type main-sequence stars with debris disk properties assessed using Herschel observations of an unbiased survey of nearby stars. Hot stars are not as commonly observed, given their unique constraints in data reduction, lack of metal lines, and "astrophysical noise" from rotation speed. Here, we address that deficiency using new and archival spectra of 83 AF-type stars. We measure the abundances of a few species in addition to Fe in order to classify the stars with Ap/Am or Lambda Boo signatures. Lambda Boo stars have a chemical signature of solar-abundant volatile species and sub-solar refractory abundances that is hypothesized to be altered by the pollution of volatiles. Overall, we see no correlation between debris disks and metallicity, primarily because the sample size is cut significantly when using only reliable fits to the spectroscopic data. The abundance measured from the Mg ii 4481 blend is a useful diagnostic because it can be reliably measured at large vcenterdotsin(i) and is found to be lower around stars with bright debris disks. We find that Lambda Boo stars have brighter debris disks compared to a bias-free sample of AF stars. The trend with disk brightness and Mg abundances suggests pollution effects can be significant and used as a marker for the stability of planetary systems. We explore trends with other species, such as with the C/O ratios, but are significantly limited by the low number of reliable detections.Peer reviewed: YesNRC publication: Ye
Brown and black carbon emitted by a marine engine operated on heavy fuel oil and distillate fuels: optical properties, size distributions, and emission factors
No full textWe characterized the chemical composition and optical properties of particulate matter (PM) emitted by a marine diesel engine operated on heavy fuel oil (HFO), marine gas oil (MGO), and diesel fuel (DF). For all three fuels, 3c80% of submicron PM was organic (and sulfate, for HFO at higher engine loads). Emission factors varied only slightly with engine load. Refractory black carbon (rBC) particles were not thickly coated for any fuel; rBC was therefore externally mixed from organic and sulfate PM. For MGO and DF PM, rBC particles were lognormally distributed in size (mode at drBC 48120\u2009nm). For HFO, much larger rBC particles were present. Combining the rBC mass concentrations with in situ absorption measurements yielded an rBC mass absorption coefficient MACBC,780nm of 7.8 \ub1 1.8 m2/g at 780 nm for all three fuels. Using positive deviations of the absorption \uc5ngstr\uf6m exponent (AAE) from unity to define brown carbon (brC), we found that brC absorption was negligible for MGO or DF PM (AAE(370,880\u2009nm) 481.0 \ub1 0.1) but typically 50% of total 370\u2010nm absorption for HFO PM. Even at 590\u2009nm, 3c20\u2009 of the total absorption was due to brC. Using absorption at 880\u2009nm as a reference for BC absorption and normalizing to organic PM mass, we obtained a MACOM,370nm of 0.4 m2/g at typical operating conditions. Furthermore, we calculated an imaginary refractive index of (0.045 \ub1 0.025)(\u3bb/370nm) 123 for HFO PM at 370\u2009nm>\u3bb > 660\u2009nm, more than twofold greater than previous recommendations. Climate models should account for this substantial brC absorption in HFO PM.Peer reviewed: YesNRC publication: Ye
Performance evaluation of phage-displayed synthetic human single-domain antibody libraries: a retrospective analysis
No full textFully human synthetic single-domain antibodies (sdAbs) are desirable therapeutic molecules but their development is a considerable challenge. Here, using a retrospective analysis of in-house historical data, we examined the parameters that impact the outcome of screening phage-displayed synthetic human sdAb libraries to discover antigen-specific binders. We found no evidence for a differential effect of domain type (VH or VL), library randomization strategy, incorporation of a stabilizing disulfide linkage or sdAb display format (monovalent vs. multivalent) on the probability of obtaining any antigen-binding human sdAbs, instead finding that the success of library screens was primarily related to properties of target antigens, especially molecular mass. The solubility and binding affinity of sdAbs isolated from successful screens depended both on properties of the sdAb libraries (primarily domain type) and the target antigens. Taking attrition of sdAbs with major manufacturability concerns (aggregation; low expression) and sdAbs that do not recognize native cell-surface antigens as independent probabilities, we calculate the overall likelihood of obtaining 651 antigen-binding human sdAb from a single library-target screen as ~24%. Successful library-target screens should be expected to yield ~1.3 human sdAbs on average, each with average binding affinity of ~2\u202f\u3bcM.Peer reviewed: YesNRC publication: Ye
Perturbing laser field dependent high harmonic phase modulations
No full textA perturbing laser pulse modulates and controls the phase of the high harmonic radiation driven by an intense fundamental pulse. Thus, a structured wave front can impress a specific spatial phase onto the generated high harmonic wave front. This modulation procedure leads to all-optical spatial light modulators for VUV or XUV radiation created by high harmonic generation. Here, through theoretical analysis and experiment, we study the correlation between the high harmonic phase modulations and the perturbing laser field amplitude and phase, providing guidelines for practical high harmonic spatial light modulators. In addition, we show that the petahertz optical oscilloscope for measuring electric fields of a perturbing beam is most robust using low order harmonics, far from the cut-off.Peer reviewed: YesNRC publication: Ye
Revisiting the extended schmidt law: the important role of existing stars in regulating star formation
No full textPeer reviewed: YesNRC publication: Ye
Sources of variance in BC mass measurements from a small marine engine: influence of the instruments, fuels and loads
No full textKnowledge of black carbon (BC) emission factors from ships is important from human health and environmental perspectives. A study of instruments measuring BC and fuels typically used in marine operation was carried out on a small marine engine. Six analytical methods measured the BC emissions in the exhaust of the marine engine operated at two load points (25% and 75%) while burning one of three fuels: a distillate marine (DMA), a low sulfur, residual marine (RMB-30) and a high-sulfur residual marine (RMG-380). The average emission factors with all instruments increased from 0.08 to 1.88 gBC/kg fuel in going from 25 to 75% load. An analysis of variance (ANOVA) tested BC emissions against instrument, load, and combined fuel properties and showed that both engine load and fuels had a statistically significant impact on BC emission factors. While BC emissions were impacted by the fuels used, none of the fuel properties investigated (sulfur content, viscosity, carbon residue and CCAI) was a primary driver for BC emissions. Of the two residual fuels, RMB-30 with the lower sulfur content, lower viscosity and lower residual carbon, had the highest BC emission factors. BC emission factors determined with the different instruments showed a good correlation with the PAS values with correlation coefficients R2 >0.95. A key finding of this research is the relative BC measured values were mostly independent of load and fuel, except for some instruments in certain fuel and load combinations.Peer reviewed: YesNRC publication: Ye
Strong-field optoelectronics in solids
No full textPerturbative optical nonlinearities induced by static electric fields have proven useful in visualizing dynamical function in systems including operating circuits, electric and magnetic domain walls, and biological matter, and in controlling light for applications in silicon photonics. Here, we extend field-induced second-harmonic generation to the non-perturbative regime. We demonstrate that static or transient fields up to terahertz (THz) frequencies applied to silicon and ZnO crystals generate even-order high harmonics. Images of the even harmonics confirm that static fields delivered with conventional electronics control the spatial properties of the high-harmonic emission. Extending our methodology to higher-harmonic photon energies paves the way for realizing active optics in the extreme ultraviolet and will allow imaging of operating electronic circuits, of Si-photonic devices and of other functional materials, with higher spatio-temporal resolution than perturbative methods. For THz spectroscopy, our method has the bandwidth to allow measurement of attosecond transients imprinted on THz waveforms.Peer reviewed: YesNRC publication: Ye
Resolved millimeter observations of the HR 8799 debris disk
No full textWe present 1.3 mm observations of the debris disk surrounding the HR 8799 multi-planet system from the Submillimeter Array to complement archival ALMA observations that spatially filtered away the bulk of the emission. The image morphology at 3".8 (150 au) resolution indicates an optically thin circumstellar belt, which we associate with a population of dust-producing planetesimals within the debris disk. The interferometric visibilities are fit well by an axisymmetric radial power-law model characterized by a broad width, \u394R/R > 48 1. The belt inclination and orientation parameters are consistent with the planet orbital parameters within the mutual uncertainties. The models constrain the radial location of the inner edge of the belt to Rin = 104(^+8 -12) au. In a simple scenario where the chaotic zone of the outermost planet b truncates the planetesimal distribution, this inner edge location translates into a constraint on the planet b mass of Mpl = 5.8^(+7.9 -3.1) M Jup. This mass estimate is consistent with infrared observations of the planet luminosity and standard hot-start evolutionary models, with the uncertainties allowing for a range of initial conditions. We also present new 9 mm observations of the debris disk from the Very Large Array and determine a millimeter spectral index of 2.41 \ub1 0.17. This value is typical of debris disks and indicates a power-law index of the grain size distribution q = 3.27 \ub1 0.10, close to predictions for a classical collisional cascade.Peer reviewed: YesNRC publication: Ye
Superior performance of Na7V4(P2O7)4PO4 in sodium ion batteries
No full textA novel synthetic method has been investigated to fabricate a 1D nanostructure Na7V4(P2O7)4PO4. Mixed polyanion materials with a well-defined 3D framework channel can improve the electrochemical performance of sodium reversible insertion/extraction reactions, and can be especially beneficial for high rate performance and cycling capability. It approaches an initial reversible electrochemical capacity of 92.0 mA h g 121 with a high discharge potential over 3.85 V (vs. Na/Na+) and good cycling properties with a capacity retention of 81.4% after 300 cycles at a 0.5C rate in sodium systems. Taking into consideration the superior electrochemical characteristics, the phase-pure composite is considered to have a promising high rate capability as well as being a high capacity electrode material for advanced energy storage applications.Peer reviewed: YesNRC publication: Ye