TNFα-Induced LDL Cholesterol Accumulation Involve Elevated LDLR Cell Surface Levels and SR-B1 Downregulation in Human Arterial Endothelial Cells

Excess lipid droplets are frequently observed in arterial endothelial cells at sites of advanced atherosclerotic plaques. Here, the role of tumor necrosis factor alpha (TNFα) in modulating the low-density lipoprotein (LDL) content in confluent primary human aortic endothelial cells (pHAECs) was investigated. TNFα promoted an up to 2 folds increase in cellular cholesterol, which was resistant to ACAT inhibition. The cholesterol increase was associated with increased ¹²⁵I-LDL surface binding. Using the non-hydrolysable label, Dil, TNFα could induce a massive increase in Dil-LDL by over 200 folds. The elevated intracellular Dil-LDL was blocked with excess unlabeled LDL and PCSK9, but not oxidized LDL (oxLDL), or apolipoprotein (apoE) depletion. Moreover, the TNFα-induced increase of LDL-derived lipids was elevated through lysosome inhibition. Using specific LDLR antibody, the Dil-LDL accumulation was reduced by over 99%. The effects of TNFα included an LDLR cell surface increase of 138%, and very large increases in ICAM-1 total and surface proteins, respectively. In contrast, that of scavenger receptor B1 (SR-B1) was reduced. Additionally, LDLR antibody bound rapidly in TNFα-treated cells by about 30 folds, inducing a migrating shift in the LDLR protein. The effect of TNFα on Dil-LDL accumulation was inhibited by the antioxidant tetramethythiourea (TMTU) dose-dependently, but not by inhibitors against NF-κB, stress kinases, ASK1, JNK, p38, or apoptosis caspases. Grown on Transwell inserts, TNFα did not enhance apical to basolateral LDL cholesterol or Dil release. It is concluded that TNFα promotes LDLR functions through combined increase at the cell surface and SR-B1 downregulation.     

Disaggregate energy consumption and industrial production in South Africa

This paper tries to assess the relationship between disaggregate energy consumption and industrial output in South Africa by undertaking a cointegration analysis using annual data from 1980 to 2005. We also investigate the causal relationships between the various disaggregate forms of energy consumption and industrial production. Our results imply that industrial production and employment are long-run forcing variables for electricity consumption. Applying the [Toda, H.Y., Yamamoto, T., 1995. Statistical inference in vector autoregressions with possibly integrated processes. Journal of Econometrics 66, 225–250] technique to Granger-causality, we find bi-directional causality between oil consumption and industrial production. For the other forms of energy consumption, there is evidence in support of the energy neutrality hypothesis. There is also evidence of causality between employment and electricity consumption as well as coal consumption causing employment.     

Optimal design of conical springs

Mechanical systems often use springs to store energy though their axial length must sometimes be significantly reduced. This leads to the use of conical springs as they are able to telescope. Designers of mechanical systems can call on a large number of tools to assist them though most of these are merely validation tools requiring concomitant trial and error strategies. Optimization strategies can be applied to provide synthesis assistance tools for which the designer simply specifies his requirement. Thus the tool directly indicates the spring best suited to standards and requirements. Recent advances in the study of constant pitch conical springs have provided analytical expressions of their behavior even in the non-linear phase. Considering this, we have used optimization strategies to provide a synthesis tool for conical spring design. An example of application is presented. The tool introduced here is thus a synthesis assistance tool that can be of considerable interest for designers who require a conical spring in their design.     

Reynolds stress and turbulence estimates in bottom boundary layer of Fall of Warness

A broadband acoustic Doppler current profiler (ADCP) moored on the seabed at 42 m depth has been used to observe the mean and turbulent flow components in the tidally energetic Fall of Warness channel over two tidal cycles. The Reynolds stress has been estimated from the difference in variance between the along-beam velocities of opposing acoustic beams. Near bed stress at 2.63 m above seabed (mab) exceeds 7.5 Pa at the time of mean flow (speed of ~ 1.3 m s^− 1) while the ebb stresses are limited to ~ 3.31 Pa during the peak ebb, mean, flow of ~ 1.3 m s^− 1. The production of turbulent kinetic energy (TKE), P was found to be negative below 2 × 10^− 9 W m^− 3 and up to 6 × 10^− 4 W m^− 3 was estimated during flood flows and decreasing to 3 × 10^− 4 W m^− 3. The TKE dissipation rate ε was estimated by inertial dissipation method (IDM) with the greatest value of 2.43 × 10^− 2 W m^− 3 observed near the seabed around maximum ebb, falling to 5.75 × 10^− 5 W m^− 3 around slack water. The comparison between P and ε was performed by calculating individual ratios of P corresponding to ε using a bootstrap resampling technique. The study shows that the ratio ε/P averaged over whole flood and ebb were found to be ~ 0.4138 and ~ 0.4177, respectively, indicating that production exceeded dissipation. The uncertainties in Reynolds stress estimates due to instrument noise were found to be 3 × 10^− 4 Pa while 4.52 × 10^− 2 Pa can be attributed to the uncertainties due to the increase in the flow-related component.     

Experimental investigation on the combustion behaviour of pre-dried Greek lignite

The present paper includes the results of the combustion tests with Greek dried lignite performed at a 1 MWth semi industrial scale pulverized coal combustion facility. Scope of the campaign is the investigation of the combustion behaviour of Greek lignite, i.e. temperature fields, ignition, burnout, emissions, as well as slagging and fouling tendency, while firing with varying levels of recirculated flue gas. Dry coal co-firing conditions in a large scale boiler are simulated by adjusting the volume flow of recirculated flue gas.Two test series representing different boiler operation modes are performed. During the first series the maximum flue gas temperature increase, when co-firing dry coal, is determined, while in the second test series the needed load decrease, in order to keep constant furnace outlet temperature in dry coal co-firing conditions is recorded. A detailed measurement set is carried out including temperature profiles, emissions, fuel, fly ash sampling and slagging and fouling investigations through the installation of dedicated deposition probes.The anticipated increase of the furnace temperature profiles by decreasing the inserted recirculated flue gas is confirmed by the experimental results. No clear trend of dry coal co-combustion on the emissions' behaviour is noticed, while dry coal firing appears to have a moderate effect on the deposition behaviour of Greek lignite. These preliminary investigations indicate that no significant operational problems are expected during a potential future demonstration of dry lignite co-firing in a Greek large scale boiler.     

Aequorin-based functional assays for G-protein-coupled receptors,ion channels,and tyrosine kinase receptors

Aequorin is a photoprotein originating from jellyfish, whose luminescent activity is dependent on the concentration of calcium ions. Due to the high sensitivity and low background linked to luminescent assays, as well as to its absence of toxicity and its large linear dynamic range, aequorin has been used as an intracellular calcium indicator since its discovery in the early 1960s. The first applications of aequorin involved its microinjection in cells. The cloning of its gene in 1985 opened the way to the stable expression of aequorin in cell lines or even entire organisms. Here we present the validation of aequorin as a functional assay for the screening of G-protein-coupled receptors, ion channels, and tyrosine kinase receptors, as well as for their pharmacological characterization in agonist and antagonist detection assays. We optimized our cell suspension-based assay and determined that the most sensitive assay was performed at room temperature, with mitochondrially expressed aequorin and using coelenterazine derivative h for reconstitution of aequorin. The robustness of the assay and the current availability of luminometers with integrated injectors allow aequorin to fit perfectly with high throughput functional assays requirements.     

Population computation of vectorial transformations

Many neurons of the central nervous system are broadly tuned to some sensory or motor variables. This property allows one to assign to each neuron a preferred attribute (PA). The width of tuning curves and the distribution of PAs in a population of neurons tuned to a given variable define the collective behavior of the population. In this article, we study the relationship of the nature of the tuning curves, the distribution of PAs, and computational properties of linear neuronal populations. We show that noise-resistant distributed linear algebraic processing and learning can be implemented by a population of cosine tuned neurons assuming a nonuniform but regular distribution of PAs. We extend these results analytically to the noncosine tuning and uniform distribution case and show with a numerical simulation that the results remain valid for a nonuniform regular distribution of PAs for broad noncosine tuning curves. These observations provide a theoretical basis for modeling general nonlinear sensorimotor transformations as sets of local linearized representations.     

A Unifying and Rigorous Shape from Shading Method Adapted to Realistic Data and Applications

We propose a new method for the Lambertian Shape From Shading (SFS) problem based on the notion of Crandall-Lions viscosity solution. This method has the advantage of requiring the knowledge of the solution (the surface to be reconstructed) only on some part of the boundary and/or of the singular set (the set of the points at maximal intensity). Moreover it unifies in an unique mathematical formulation the works of Rouy et al. [34, 50], Falcone et al. [21], Prados et al. [46, 48, 49], based on the notion of viscosity solutions and the work of Dupuis and Oliensis [17] dealing with classical solutions and value functions. Also, it allows to generalize their results to the “perspective SFS” problem recently simultaneously introduced in [13,46,55]. While the theoretical part has been developed in [44], in this paper we give some stability results and we describe numerical schemes for the SFS based on this method. We construct provably convergent and robust algorithms. Finally, we apply our SFS method to real images and we suggest some real-life applications.