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.     

Intelligent synthetic composite indicators with application

This article is proposing an alternative approach to develop Intelligent Synthetic Composite Indicators (ISCI). The suggested approach utilizes Fuzzy Proximity Knowledge Mining technique to build the qualitative taxonomy initially, and then Fuzzy c-means is employed to form the new composite indicators. A fully worked application is presented. The application uses Information and Communication Technology real variables to form a new unified ICT index, illustrating the method of construction for ISCI. The weighting and aggregation results obtained were compared against Principal Component Analysis, Factor Analysis and the Geometric mean to weight and aggregate synthetic composite indicators. This study also compares and contrasts two special Fuzzy c-means techniques that is, the Optimal Completion Strategy and the Nearest Prototype Strategy to impute missing values. The results are compared against statistical imputation techniques. The validity and robustness of all techniques are evaluated using Monte Carlo simulation. The results obtained suggest a novel, intelligent and non-biased method of building future composite indicators.     

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.     

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.     

A Human Aware Mobile Robot Motion Planner

Robot navigation in the presence of humans raises new issues for motion planning and control when the humans must be taken explicitly into account. We claim that a human aware motion planner (HAMP) must not only provide safe robot paths, but also synthesize good, socially acceptable and legible paths. This paper focuses on a motion planner that takes explicitly into account its human partners by reasoning about their accessibility, their vision field and their preferences in terms of relative human-robot placement and motions in realistic environments. This planner is part of a human-aware motion and manipulation planning and control system that we aim to develop in order to achieve motion and manipulation tasks in the presence or in synergy with humans.     

A parallel coordinates style interface for exploratory volume visualization

We present a user interface, based on parallel coordinates, that facilitates exploration of volume data. By explicitly representing the visualization parameter space, the interface provides an overview of rendering options and enables users to easily explore different parameters. Rendered images are stored in an integrated history bar that facilitates backtracking to previous visualization options. Initial usability testing showed clear agreement between users and experts of various backgrounds (usability, graphic design, volume visualization, and medical physics) that the proposed user interface is a valuable data exploration tool.