14,744 research outputs found
High altitude gust acceleration environment as experienced by a supersonic airplane
High altitude turbulence experienced at supersonic speeds is described in terms of gust accelerations measured on the YF-12A airplane. The data were obtained during 90 flights at altitudes above 12.2 kilometers (40,000 feet). Subjective turbulence intensity ratings were obtained from air crew members. The air crew often rated given gust accelerations as being more intense during high altitude supersonic flight than during low altitude subsonic flight. The portion of flight distance in turbulence ranged from 6 percent to 8 percent at altitudes between 12.2 kilometers and 16.8 kilometers (40,000 feet and 55,000 feet) to less than 1 percent at altitudes above 18.3 kilometers (60,000 feet). The amount of turbulence varied with season, increasing by a factor of 3 or more from summer to winter. Given values of gust acceleration were less frequent, on the basis of distance traveled, for supersonic flight of the YF-12A airplane at altitudes above 12.2 kilometers (40,000 feet) than for subsonic flight of a jet passenger airplane at altitudes below 12.2 kilometers (40,000 feet). The median thickness of high altitude turbulence patches was less than 400 meters (1300 feet); the median length was less than 16 kilometers (10 miles). The distribution of the patch dimensions tended to be log normal
A concept for reducing oceanic separation minima through the use of a TCAS-derived CDTI
A concept for using a cockpit display of traffic information (CDTI), as derived from a modified version of the Traffic Alert and Collision Avoidance System 2 (TCAS 2), to support reductions in air traffic separation minima for an oceanic track system is presented. The concept, and the TCAS modifications required to support it, are described. The feasibility of the concept is examined from a number of standpoints, including expected benefits, maximum alert rates, and possible transition strategies. Various implementation issues are analyzed. Pilot procedures are suggested for dealing with alert situations. Possible variations of the concept are also examined. Finally, recommendations are presented for other studies and simulation experiments which can be used to further verify the feasibility of the concept
A designed protein interface that blocks fibril formation
Protein fibril formation is implicated in many diseases, and therefore much effort has been focused toward the development of inhibitors of this process. In a previous project, a monomeric protein was computationally engineered to bind itself and form a heterodimer complex following interfacial redesign. One of the protein monomers, termed monomer-B, was unintentionally destabilized and shown to form macroscopic fibrils. Interestingly, in the presence of the designed binding partner, fibril formation was blocked. Here we describe the complete characterization of the amyloid properties of monomer-B and the inhibition of fiber formation by the designed binding partner, monomer-A. Both proteins are mutants of the betal domain of streptococcal protein-G. The free monomer-B protein forms amyloid-type fibrils, as determined by transmission electron microscopy and the change in fluorescence of Thioflavin T, an amyloid-specific dye. Fibril formation kinetics are influenced by pH, protein concentration, and seeding with preformed fibrils. Under all conditions tested, monomer-A was able to inhibit the formation of monomer-B fibrils. This inhibition is specific to the engineered interaction, as incubation of monomer-B with wild-type protein-G (a structural homologue) did not result in inhibition under the same conditions. Thus, this de novo-designed heterodimeric complex is an excellent model system for the study of protein-based fibril formation and inhibition. This system provides additional insight into the development of pharmaceuticals for amyloid disorders, as well as the potential use of amyloid fibrils for self-assembling nanostructures
Space shuttle abort separation pressure investigation. Volume 2, Part B: Orbiter data at Mach 5
For abstract, see
Rational design of expression vectors for high quality biologics
Commercial proteins (e.g. antibodies, enzymes, vaccine components) for applications from biopharmaceuticals to commodity chemicals require low-cost manufacturing of high-quality products. The engineering of recombinant hosts to achieve large quantities of high-quality heterologous proteins is crucial to both minimizing costs and maximizing safety and efficacy (in the case of biopharmaceuticals). High-quality proteins are properly folded and full-length (intact), with native N-, and C-, termini and bear no significant proteolysis or other degradation (oxidation, deamidation, etc…). As most expression hosts rely on recombinant DNA technology for production of the heterologous protein, the transgene cassette provides an early, and inexpensive, opportunity for optimization of quality and protein titer. Commonly, transgene cassettes include a promoter, a heterologous gene of interest, and terminator for expression of the heterologous gene. A targeting sequence for guided recombination and selective marker for isolation of positive clones are also key elements. In engineering the transgene cassette, factors such as the promoter for heterologous gene expression, target site for transgene integration, sequence for translation initiation, and mRNA codon-optimization of the gene of interest are critical design points for a given protein-expressing strain.
Here, we demonstrate an approach to transgene cassette optimization in the methylotrophic yeast, Pichia pastoris, informed by functional genomics. Omics-based techniques such as RNA-Seq, ATAC-Seq and ribosomal foot-printing afford greater upfront understanding for subsequent optimized strain engineering on a product-by-product basis. These types of data are cheap and easy to acquire for yeast and can indicate host- or sequence-derived bottlenecks in transgene transcription, translation and expression. Linking these data to product quality attributes can enlighten the design of the expression vector for fast in silico optimization of wide-ranging factors such as gene dosage balance, translation efficiency, and balanced cell kinetics enabling high-quality protein production. Collectively, we show that these tools can enable fast vector design for new heterologous protein-producing strains, including those expressing recombinant vaccines, and robust optimization when engineering higher productivity cell lines
Averaging and sampling for magnetic-observatory hourly data
A time and frequency-domain analysis is made of the effects of averaging and
sampling methods used for constructing magnetic-observatory hourly data
values. Using 1-min data as a proxy for continuous, geomagnetic variation,
we construct synthetic hourly values of two standard types: instantaneous
"spot" measurements and simple 1-h "boxcar" averages. We compare these
average-sample types with others: 2-h average, Gaussian, and "brick-wall"
low-frequency-pass. Hourly spot measurements provide a statistically unbiased
representation of the amplitude range of geomagnetic-field variation, but as
a representation of continuous field variation over time, they are
significantly affected by aliasing, especially at high latitudes. The 1-h,
2-h, and Gaussian average-samples are affected by a combination of amplitude
distortion and aliasing. Brick-wall values are not affected by either
amplitude distortion or aliasing, but constructing them is, in an operational
setting, relatively more difficult than it is for other average-sample types.
It is noteworthy that 1-h average-samples, the present standard for
observatory hourly data, have properties similar to Gaussian average-samples
that have been optimized for a minimum residual sum of amplitude distortion
and aliasing. For 1-h average-samples from medium and low-latitude
observatories, the average of the combination of amplitude distortion and
aliasing is less than the 5.0 nT accuracy standard established by Intermagnet
for modern 1-min data. For medium and low-latitude observatories, average
differences between monthly means constructed from 1-min data and monthly
means constructed from any of the hourly average-sample types considered here
are less than the 1.0 nT resolution of standard databases. We recommend that
observatories and World Data Centers continue the standard practice of
reporting simple 1-h-average hourly values
Development of a novel clinical scoring system for on-farm diagnosis of bovine respiratory disease in pre-weaned dairy calves.
Several clinical scoring systems for diagnosis of bovine respiratory disease (BRD) in calves have been proposed. However, such systems were based on subjective judgment, rather than statistical methods, to weight scores. Data from a pair-matched case-control study on a California calf raising facility was used to develop three novel scoring systems to diagnose BRD in preweaned dairy calves. Disease status was assigned using both clinical signs and diagnostic test results for BRD-associated pathogens. Regression coefficients were used to weight score values. The systems presented use nasal and ocular discharge, rectal temperature, ear and head carriage, coughing, and respiratory quality as predictors. The systems developed in this research utilize fewer severity categories of clinical signs, require less calf handling, and had excellent agreement (Kappa > 0.8) when compared to an earlier scoring system. The first scoring system dichotomized all clinical predictors but required inducing a cough. The second scoring system removed induced cough as a clinical abnormality but required distinguishing between three levels of nasal discharge severity. The third system removed induced cough and forced a dichotomized variable for nasal discharge. The first system presented in this study used the following predictors and assigned values: coughing (induced or spontaneous coughing, 2 points), nasal discharge (any discharge, 3 points), ocular discharge (any discharge, 2 points), ear and head carriage (ear droop or head tilt, 5 points), fever (≥39.2°C or 102.5°F, 2 points), and respiratory quality (abnormal respiration, 2 points). Calves were categorized "BRD positive" if their total score was ≥4. This system correctly classified 95.4% cases and 88.6% controls. The second presented system categorized the predictors and assigned weights as follows: coughing (spontaneous only, 2 points), mild nasal discharge (unilateral, serous, or watery discharge, 3 points), moderate to severe nasal discharge (bilateral, cloudy, mucoid, mucopurlent, or copious discharge, 5 points), ocular discharge (any discharge, 1 point), ear and head carriage (ear droop or head tilt, 5 points), fever (≥39.2°C, 2 points), and respiratory quality (abnormal respiration, 2 points). Calves were categorized "BRD positive" if their total score was ≥4. This system correctly classified 89.3% cases and 92.8% controls. The third presented system used the following predictors and scores: coughing (spontaneous only, 2 points), nasal discharge (any, 4 points), ocular discharge (any, 2 points), ear and head carriage (ear droop or head tilt, 5 points), fever (≥39.2°C, 2 points), and respiratory quality (abnormal respiration, 2 points). Calves were categorized "BRD positive" if their total score was ≥5. This system correctly classified 89.4% cases and 90.8% controls. Each of the proposed systems offer few levels of clinical signs and data-based weights for on-farm diagnosis of BRD in dairy calves
Nonaffine Correlations in Random Elastic Media
Materials characterized by spatially homogeneous elastic moduli undergo
affine distortions when subjected to external stress at their boundaries, i.e.,
their displacements \uv (\xv) from a uniform reference state grow linearly
with position \xv, and their strains are spatially constant. Many materials,
including all macroscopically isotropic amorphous ones, have elastic moduli
that vary randomly with position, and they necessarily undergo nonaffine
distortions in response to external stress. We study general aspects of
nonaffine response and correlation using analytic calculations and numerical
simulations. We define nonaffine displacements \uv' (\xv) as the difference
between \uv (\xv) and affine displacements, and we investigate the
nonaffinity correlation function
and related functions. We introduce four model random systems with random
elastic moduli induced by locally random spring constants, by random
coordination number, by random stress, or by any combination of these. We show
analytically and numerically that scales as A |\xv|^{-(d-2)}
where the amplitude is proportional to the variance of local elastic moduli
regardless of the origin of their randomness. We show that the driving force
for nonaffine displacements is a spatial derivative of the random elastic
constant tensor times the constant affine strain. Random stress by itself does
not drive nonaffine response, though the randomness in elastic moduli it may
generate does. We study models with both short and long-range correlations in
random elastic moduli.Comment: 22 Pages, 18 figures, RevTeX
Soft lubrication: the elastohydrodynamics of non-conforming and conforming contacts
We study the lubrication of fluid-immersed soft interfaces and show that
elastic deformation couples tangential and normal forces and thus generates
lift. We consider materials that deform easily, due to either geometry (e.g. a
shell) or constitutive properties (e.g. a gel or a rubber), so that the effects
of pressure and temperature on the fluid properties may be neglected. Four
different system geometries are considered: a rigid cylinder moving parallel to
a soft layer coating a rigid substrate; a soft cylinder moving parallel to a
rigid substrate; a cylindrical shell moving parallel to a rigid substrate; and
finally a cylindrical conforming journal bearing coated with a thin soft layer.
In addition, for the particular case of a soft layer coating a rigid substrate
we consider both elastic and poroelastic material responses. For all these
cases we find the same generic behavior: there is an optimal combination of
geometric and material parameters that maximizes the dimensionless normal force
as a function of the softness parameter = hydrodynamic pressure/elastic
stiffness = surface deflection/gap thickness which characterizes the
fluid-induced deformation of the interface. The corresponding cases for a
spherical slider are treated using scaling concepts.Comment: 61 pages, 20 figures, 2 tables, submitted to Physics of Fluid
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