Chondrule-Forming Shock Fronts in the Solar Nebula: A Possible Unified Scenario for Planet and Chondrite Formation

Chondrules are mm-sized spherules found throughout primitive, chondritic meteorites. Flash heating by a shock front is the leading explanation of their formation. However, identifying a mechanism for creating shock fronts inside the solar nebula has been difficult. In a gaseous disk capable of forming Jupiter, the disk must have been marginally gravitationally unstable at and beyond Jupiter's orbit. We show that this instability can drive inward spiral shock fronts with shock speeds of up to about 10 km/s at asteroidal orbits, sufficient to account for chondrule formation. Mixing and transport of solids in such a disk, combined with the planet-forming tendencies of gravitational instabilities, results in a unified scenario linking chondrite production with gas giant planet formation.Comment: 2 figures. ApJ Letters, in pres

Highly-accurate 5-axis flank CNC machining with conical tools

A new method for $5$-axis flank computer numerically controlled (CNC) machining using a predefined set of tappered ball-end-mill tools (aka conical) cutters is proposed. The space of lines that admit tangential motion of an associated truncated cone along a general, doubly curved, free-form surface is explored. These lines serve as discrete positions of conical axes in 3D space. Spline surface fitting is used to generate a ruled surface that represents a single continuous sweep of a rigid conical milling tool. An optimization based approach is then applied to globally minimize the error between the design surface and the conical envelope. Our computer simulation are validated with physical experiments on two benchmark industrial datasets, reducing significantly the execution times while preserving or even reducing the milling error when compared to the state-of-the-art industrial software

AA-Amyloidosis Can Be Transferred by Peripheral Blood Monocytes

Spongiform encephalopathies have been reported to be transmitted by blood transfusion even prior to the clinical onset. Experimental AA-amyloidosis shows similarities with prion disease and amyloid-containing organ-extracts can prime a recipient for the disease. In this systemic form of amyloidosis N-terminal fragments of the acute-phase reactant apolipoprotein serum amyloid A are the main amyloid protein. Initial amyloid deposits appear in the perifollicular region of the spleen, followed by deposits in the liver. We used the established murine model and induced AA-amyloidosis in NMRI mice by intravenous injections of purified amyloid fibrils (‘amyloid enhancing factor’) combined with inflammatory challenge (silver nitrate subcutaneously). Blood plasma and peripheral blood monocytes were isolated, sonicated and re-injected into new recipients followed by an inflammatory challenge during a three week period. When the animals were sacrificed presence of amyloid was analyzed in spleen sections after Congo red staining. Our result shows that some of the peripheral blood monocytes, isolated from animals with detectable amyloid, contained amyloid-seed that primed for AA-amyloid. The seeding material seems to have been phagocytosed by the cells since the AA-precursor (SAA1) was found not be expressed by the monocytes. Plasma recovered from mice with AA amyloidosis lacked seeding capacity. Amyloid enhancing activity can reside in monocytes recovered from mice with AA-amyloidosis and in a prion-like way trigger amyloid formation in conjunction with an inflammatory disorder. Human AA-amyloidosis resembles the murine form and every individual is expected to be exposed to conditions that initiate production of the acute-phase reactant. The monocyte-transfer mechanism should be eligible for the human disease and we point out blood transfusion as a putative route for transfer of amyloidosis

The study of atmospheric ice-nucleating particles via microfluidically generated droplets

Ice-nucleating particles (INPs) play a significant role in the climate and hydrological cycle by triggering ice formation in supercooled clouds, thereby causing precipitation and affecting cloud lifetimes and their radiative properties. However, despite their importance, INP often comprise only 1 in 10³–10⁶ ambient particles, making it difficult to ascertain and predict their type, source, and concentration. The typical techniques for quantifying INP concentrations tend to be highly labour-intensive, suffer from poor time resolution, or are limited in sensitivity to low concentrations. Here, we present the application of microfluidic devices to the study of atmospheric INPs via the simple and rapid production of monodisperse droplets and their subsequent freezing on a cold stage. This device offers the potential for the testing of INP concentrations in aqueous samples with high sensitivity and high counting statistics. Various INPs were tested for validation of the platform, including mineral dust and biological species, with results compared to literature values. We also describe a methodology for sampling atmospheric aerosol in a manner that minimises sampling biases and which is compatible with the microfluidic device. We present results for INP concentrations in air sampled during two field campaigns: (1) from a rural location in the UK and (2) during the UK’s annual Bonfire Night festival. These initial results will provide a route for deployment of the microfluidic platform for the study and quantification of INPs in upcoming field campaigns around the globe, while providing a benchmark for future lab-on-a-chip-based INP studies

BioSimulators: a central registry of simulation engines and services for recommending specific tools

Computational models have great potential to accelerate bioscience, bioengineering, and medicine. However, it remains challenging to reproduce and reuse simulations, in part, because the numerous formats and methods for simulating various subsystems and scales remain siloed by different software tools. For example, each tool must be executed through a distinct interface. To help investigators find and use simulation tools, we developed BioSimulators (https://biosimulators.org), a central registry of the capabilities of simulation tools and consistent Python, command-line and containerized interfaces to each version of each tool. The foundation of BioSimulators is standards, such as CellML, SBML, SED-ML and the COMBINE archive format, and validation tools for simulation projects and simulation tools that ensure these standards are used consistently. To help modelers find tools for particular projects, we have also used the registry to develop recommendation services. We anticipate that BioSimulators will help modelers exchange, reproduce, and combine simulations

Bioavailability assessment: Methods to estimate total area (AUC 0-∞) and total amount excreted (A e ∞ ) and importance of blood and urine sampling scheme with application to digoxin

Five methods are compared to estimate the total area under the digoxin plasma or serum concentrationtime curve (AUC0-∞) after a single dose of drug. To obtain accurate estimates of AUC0-∞, data required are concentrations at a sufficient number of sampling times to define adequately the concentration-time curve prior to the log-linear phase, and at least three, but preferably four or more equally spaced points in the terminal loglinear phase. One method (designated Method I) requires a digital computer; another (Method III) is the classical method (these two methods do not require equally spaced points in the loglinear phase). Method IIA is the accelerated convergence method of Amidon et al.; Methods IIB and IIC are modifications of this method, but incorporate usual and orthogonal least squares, respectively, which make them more accurate with real (noisy) data. Methods I and IICgave very comparable estimates of AUC0-∞. Results indicate that digoxin administered orally in aqueous solution was completely (100%) absorbed when bioavailability estimates were based on oral and intravenous AUC0-∞ estimates and the actual doses, whereas formerly only about 80% absorption was reported, based on areas, under plasma concentration curves which were truncated at 96 hr. It is shown that the sampling scheme of blood can produce biased apparent bioavailability estimates when areas under truncated curves are employed, but an appropriate sampling scheme and application of method IIyield accurate bioavailability estimates. This is important particularly in those bioavailability studies where one is attempting to determine the appropriate label dose for a new “fastrelease” digoxin preparation relative to the label dose and bioavailability of currently marketed tablets. It is shown that the magnitudes and variability of apparent elimination rate constants and halflives of digoxin, estimated from urinary excretion data by the σ − method, depend on which value of A e ∞ is used. The formerly reported greater interindividual variability of AUC data compared to At data for digoxin is explained in that the AUCs, but not the A e ,'s, involve the renal clearance, which exhibits considerable inter- and intraindividual variation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45073/1/10928_2005_Article_BF01061733.pd