Stimulation of bile acid synthesis by dibutyryl cyclic AMP in isolated rat hepatocytes

Freshly isolated rat hepatocytes were used to examine the effects of dibutyryl cyclic AMP on the incorporation of¹⁴C-acetate and¹⁴C-cholesterol into bile acids. After an initial lag period, both precursors were incorporated into cholic and chenodeoxycholic acids at a linear rate for the subsequent 60 min. An apparent stimulation of bile acid formation from¹⁴C-acetate by dibutyryl cyclic AMP was complicated by the concomitant inhibition of cholesterol synthesis. In experiments with¹⁴C-cholesterol, dibutyryl cyclic AMP (1 mM) increased the labeled cholic and chenodeoxycholic acids in the medium by 83 and 224%, respectively, but cellular levels of labeled bile acids were unchanged. As a result, the nucleotide stimulated the overall incorporation of¹⁴C-cholesterol into cholic acid by 39% and into chenodeoxycholic acid by 123%. The mean ratio of labeled cholic to chenodeoxycholic acid declined from 55∶45 in control cells to 41∶59 in cells incubated with dibutyryl cyclic AMP. The results demonstrate that label incorporation can be used to study the regulation of bile acid synthesis in isolated hepatocytes. We propose that dibutyryl cyclic AMP enhances bile acid production by phosphorylating, and thus stimulating the activity of, cholesterol 7α-hydroxylase, the rate-limiting enzyme in bile acid synthesis.     

An experimental and numerical analysis of the influence of the inlet temperature,equivalence ratio and compression ratio on the HCCI auto-ignition process of Primary Reference Fuels in an engine

In order to understand better the auto-ignition process in an HCCI engine, the influence of some important parameters on the auto-ignition is investigated. The inlet temperature, the equivalence ratio and the compression ratio were varied and their influence on the pressure, the heat release and the ignition delays were measured. The inlet temperature was changed from 25 to 70 °C and the equivalence ratio from 0.18 to 0.41, while the compression ratio varied from 6 to 13.5. The fuels that were investigated were PRF40 and n-heptane. These three parameters appeared to decrease the ignition delays, with the inlet temperature having the least influence and the compression ratio the most. A previously experimentally validated reduced surrogate mechanism, for mixtures of n-heptane, iso-octane and toluene, has been used to explain observations of the auto-ignition process. The same kinetic mechanism is used to better understand the underlying chemical and physical phenomena that make the influence of a certain parameter change according to the operating conditions. This can be useful for the control of the auto-ignition process in an HCCI engine.     

What makes virtual agents believable?

In this paper we investigate the concept of believability and make an attempt to isolate individual characteristics (features) that contribute to making virtual characters believable. As the result of this investigation we have produced a formalisation of believability and based on this formalisation built a computational framework focused on simulation of believable virtual agents that possess the identified features. In order to test whether the identified features are, in fact, responsible for agents being perceived as more believable, we have conducted a user study. In this study we tested user reactions towards the virtual characters that were created for a simulation of aboriginal inhabitants of a particular area of Sydney, Australia in 1770 A.D. The participants of our user study were exposed to short simulated scenes, in which virtual agents performed some behaviour in two different ways (while possessing a certain aspect of believability vs. not possessing it). The results of the study indicate that virtual agents that appear resource bounded, are aware of their environment, own interaction capabilities and their state in the world, agents that can adapt to changes in the environment and exist in correct social context are those that are being perceived as more believable. Further in the paper we discuss these and other believability features and provide a quantitative analysis of the level of contribution for each such feature to the overall perceived believability of a virtual agent.     

A Microstructure-Based Time-Dependent Crack Growth Model for Life and Reliability Prediction of Turbopropulsion Systems

The objective of this investigation was to develop an innovative methodology for life and reliability prediction of hot-section components in advanced turbopropulsion systems. A set of generic microstructure-based time-dependent crack growth (TDCG) models was developed and used to assess the sources of material variability due to microstructure and material parameters such as grain size, activation energy, and crack growth threshold for TDCG. A comparison of model predictions and experimental data obtained in air and in vacuum suggests that oxidation is responsible for higher crack growth rates at high temperatures, low frequencies, and long dwell times, but oxidation can also induce higher crack growth thresholds (ΔK _th or K _th) under certain conditions. Using the enhanced risk analysis tool and material constants calibrated to IN 718 data, the effect of TDCG on the risk of fracture in turboengine components was demonstrated for a generic rotor design and a realistic mission profile using the DARWIN^® probabilistic life-prediction code. The results of this investigation confirmed that TDCG and cycle-dependent crack growth in IN 718 can be treated by a simple summation of the crack increments over a mission. For the temperatures considered, TDCG in IN 718 can be considered as a K-controlled or a diffusion-controlled oxidation-induced degradation process. This methodology provides a pathway for evaluating microstructural effects on multiple damage modes in hot-section components.     

On partitioning rectilinear polygons into star-shaped polygons

We present an algorithm for finding optimum partitions of simple monotone rectilinear polygons into star-shaped polygons. The algorithm may introduce Steiner points and its time complexity isO(n), wheren is the number of vertices in the polygon. We then use this algorithm to obtain anO(n logn) approximation algorithm for partitioning simple rectilinear polygons into star-shaped polygons with the size of the partition being at most six times the optimum.     

Molecular Classification and Pharmacogenetics of Primary Plasma Cell Leukemia: An Initial Approach toward Precision Medicine

Primary plasma cell leukemia (pPCL) is a rare and aggressive variant of multiple myeloma (MM) which may represent a valid model for high-risk MM. This disease is associated with a very poor prognosis, and unfortunately, it has not significantly improved during the last three decades. New high-throughput technologies have allowed a better understanding of the molecular basis of this disease and moved toward risk stratification, providing insights for targeted therapy studies. This knowledge, added to the pharmacogenetic profile of new and old agents in the analysis of efficacy and safety, could contribute to help clinical decisions move toward a precision medicine and a better clinical outcome for these patients. In this review, we describe the available literature concerning the genomic characterization and pharmacogenetics of plasma cell leukemia (PCL).     

Anisotropic Properties of Quasi-1D In4Se3: Mechanical Exfoliation,Electronic Transport,and Polarization-Dependent Photoresponse

Theoretical and experimental investigations of various exfoliated samples taken from layered In₄Se₃ crystals are performed. In spite of the ionic character of interlayer interactions in In₄Se₃ and hence much higher calculated cleavage energies compared to graphite, it is possible to produce few-nanometer-thick flakes of In₄Se₃ by mechanical exfoliation of its bulk crystals. The In₄Se₃ flakes exfoliated on Si/SiO₂ have anisotropic electronic properties and exhibit field-effect electron mobilities of about 50 cm² V⁻¹ s⁻¹ at room temperature, which are comparable with other popular transition metal chalcogenide (TMC) electronic materials, such as MoS₂ and TiS₃. In₄Se₃ devices exhibit a visible range photoresponse on a timescale of less than 30 ms. The photoresponse depends on the polarization of the excitation light consistent with symmetry-dependent band structure calculations for the most expected ac cleavage plane. These results demonstrate that mechanical exfoliation of layered ionic In₄Se₃ crystals is possible, while the fast anisotropic photoresponse makes In₄Se₃ a competitive electronic material, in the TMC family, for emerging optoelectronic device applications.     

Numerical Analysis of Flexible Multibody Systems

Flexible multibody systems featurea coupled mathematical model with ODEs or DAEs governing the gross motion and PDEs describing the elastic deformation of particular bodies.Frequently, semidiscretization of elastic members leads to a stiff mechanical system with widely different time scales. Thispaper investigates the behavior of numerical time integration methodsat flexible multibody systems and gives some recommendations.Simulation results for a slider crank mechanism and a truck modelillustrate what can go wrong and how implicit methods like RADAU5 can beeffectively applied.     

On comparisons of random, partition, and proportional partitiontesting

Early studies of random versus partition testing used the probability of detecting at least one failure as a measure of test effectiveness and indicated that partition testing is not significantly more effective than random testing. More recent studies have focused on proportional partition testing because a proportional allocation of the test cases (according to the probabilities of the subdomains) can guarantee that partition testing will perform at least as well as random testing. We show that this goal for partition testing is not a worthwhile one. Guaranteeing that partition testing has at least as high a probability of detecting a failure comes at the expense of decreasing its relative advantage over random testing. We then discuss other problems with previous studies and show that failure to include important factors (cost, relative effectiveness) can lead to misleading results     

A finite volume method on NURBS geometries and its application in isogeometric fluid–structure interaction

A finite volume method for geometries parameterized by Non-Uniform Rational B-Splines (NURBS) is proposed. Since the computational grid is inherently defined by the knot vectors of the NURBS parameterization, the mesh generation step simplifies here greatly and furthermore curved boundaries are resolved exactly. Based on the incompressible Navier–Stokes equations, the main steps of the discretization are presented, with emphasis on the preservation of geometrical and physical properties. Moreover, the method is combined with a structural solver based on isogeometric finite elements in a partitioned fluid–structure interaction coupling algorithm that features a gap-free and non-overlapping interface even in the case of non-matching grids.