Foam Cells as Therapeutic Targets in Atherosclerosis with a Focus on the Regulatory Roles of Non-Coding RNAs

Atherosclerosis is a major cause of human cardiovascular disease, which is the leading cause of mortality around the world. Various physiological and pathological processes are involved, including chronic inflammation, dysregulation of lipid metabolism, development of an environment characterized by oxidative stress and improper immune responses. Accordingly, the expansion of novel targets for the treatment of atherosclerosis is necessary. In this study, we focus on the role of foam cells in the development of atherosclerosis. The specific therapeutic goals associated with each stage in the formation of foam cells and the development of atherosclerosis will be considered. Processing and metabolism of cholesterol in the macrophage is one of the main steps in foam cell formation. Cholesterol processing involves lipid uptake, cholesterol esterification and cholesterol efflux, which ultimately leads to cholesterol equilibrium in the macrophage. Recently, many preclinical studies have appeared concerning the role of non-encoding RNAs in the formation of atherosclerotic lesions. Non-encoding RNAs, especially microRNAs, are considered regulators of lipid metabolism by affecting the expression of genes involved in the uptake (e.g., CD36 and LOX1) esterification (ACAT1) and efflux (ABCA1, ABCG1) of cholesterol. They are also able to regulate inflammatory pathways, produce cytokines and mediate foam cell apoptosis. We have reviewed important preclinical evidence of their therapeutic targeting in atherosclerosis, with a special focus on foam cell formation.     

Morphological,Anatomical, and Phytochemical Studies of Carlina acaulis L. Cypsela

Carlina acaulis L. has a long tradition of use in folk medicine. The chemical composition of the roots and green parts of the plant is quite well known. There is the lowest amount of data on the cypsela (fruit) of this plant. In this study, the microscopic structures and the chemical composition of the cypsela were investigated. Preliminary cytochemical studies of the structure of the Carlina acaulis L. cypsela showed the presence of substantial amounts of protein and lipophilic substances. The chemical composition of the cypsela was investigated using spectrophotometry, gas chromatography with mass spectrometry, and high-performance liquid chromatography with spectrophotometric and fluorescence detection. The cypsela has been shown to be a rich source of macro- and microelements, vegetable oil (25%), α-tocopherol (approx. 2 g/kg of oil), protein (approx. 36% seed weight), and chlorogenic acids (approx. 22 g/kg seed weight). It also contains a complex set of volatile compounds. The C. acaulis cypsela is, therefore, a valuable source of nutrients and bioactive substances.     

Biochemical Characterization of Recombinant UDPG-Dependent IAA Glucosyltransferase from Maize (Zea mays)

Here, we report a biochemical characterization of recombinant maize indole-3-acetyl-β-d-glucose (IAGlc) synthase which glucosylates indole-3-acetic acid (IAA) and thus abolishes its auxinic activity affecting plant hormonal homeostasis. Substrate specificity analysis revealed that IAA is a preferred substrate of IAGlc synthase; however, the enzyme can also glucosylate indole-3-butyric acid and indole-3-propionic acid with the relative activity of 66% and 49.7%, respectively. K_M values determined for IAA and UDP glucose are 0.8 and 0.7 mM, respectively. 2,4-Dichlorophenoxyacetic acid is a competitive inhibitor of the synthase and causes a 1.5-fold decrease in the enzyme affinity towards IAA, with the K_i value determined as 117 μM, while IAA–Asp acts as an activator of the synthase. Two sugar-phosphate compounds, ATP and glucose-1-phosphate, have a unique effect on the enzyme by acting as activators at low concentrations and showing inhibitory effect at higher concentrations (above 0.6 and 4 mM for ATP and glucose-1-phosphate, respectively). Results of molecular docking revealed that both compounds can bind to the PSPG (plant secondary product glycosyltransferase) motif of IAGlc synthase; however, there are also different potential binding sites present in the enzyme. We postulate that IAGlc synthase may contain more than one binding site for ATP and glucose-1-phosphate as reflected in its activity modulation.     

Characterization of multiphase gas–solid flow and accuracy of turbulence models for lower stage cyclones used in suspension preheaters

This study involved the analysis and characterization of the multiphase flow phenomenon inside the lower stage cyclone separator used in the clinker burning process. The analysis was performed using both CFD and experimental research methods. Very few studies are devoted to such types of cyclone separators, which in addition to their basic functions are also responsible for the technological process. Due to the atypical working conditions of these cyclone separators, they are characterized with a complex geometry, which significantly differs from that of the traditional separators.Furthermore, the evaluation of the accuracy and level of reliability of the two models of turbulence closure—k-e RNG and RSM(RANS), and the LES. The results obtained led to the conclusion that for the lower stage cyclone separators, the LES model proved to be the most accurate(both in the case of forecasting the separation efficiency and pressure drop). The performance parameter(in particular the separation efficiency) values obtained for the RSM model were also characterized by high accuracy. The k-e RNG model was characterized by significantly larger deviations.     

On asymptotic stability of linear time-varying infinite-dimensional systems

It is shown that every asymptotically equistable linear time-varying infinite-dimensional discrete-time system x_k+1 = A_kx_k is uniformly asymptotically equistable, if A_k is a collectively compact sequence of bounded linear operators. Next, this result is used to prove that for a broad class of linear retarded functional differential equations, the notions of asymptotic equistability and uniform asymptotic equistability coincide.     

Ultrafast Torsional Relaxation from the Barrier Region for an Excited-State Isomerization in Solution: 9-Carbonylanthracenes

The class of compounds containing a carbonyl group substituted at the 9 position of anthracene have been studied as new model systems for torsional isomerization in solution. Franck-Condon excitation yields an excited-state distribution near the barrier for isomerization in S₁. Using time-resolved fluorescence spectroscopy, we have determined that the relaxation from the barrier region is subpicosecond for three different compounds in all solvents studied. In fact, the relaxation seems to be almost independent of solvent at room temperature, indicating that most of the local friction felt by the twisting carbonyl is internal friction rather than solvent friction. Apparently the small carbonyl is effectively shielded from the solvent by the anthracene ring so the solvent friction is not strong. In contrast to the weak solvent coupling, previously reported gas-phase spectra indicate that the torsion may be strongly coupled to the other vibrational modes of the molecule. Energy flow out of the torsion into these other vibrational modes appears to occur on the subpicosecond time scale.     

Boosting Room‐Temperature Magneto‐Ionics in a Non‐Magnetic Oxide Semiconductor

Voltage control of magnetism through electric field‐induced oxygen motion (magneto‐ionics) could represent a significant breakthrough in the pursuit for new strategies to enhance energy efficiency in magnetically actuated devices. Boosting the induced changes in magnetization, magneto‐ionic rates and cyclability continue to be key challenges to turn magneto‐ionics into real applications. Here, it is demonstrated that room‐temperature magneto‐ionic effects in electrolyte‐gated paramagnetic Co₃O₄ films can be largely increased both in terms of generated magnetization (6 times larger) and speed (35 times faster) if the electric field is applied using an electrochemical capacitor configuration (utilizing an underlying conducting buffer layer) instead of placing the electric contacts at the side of the semiconductor (electric‐double‐layer transistor‐like configuration). This is due to the greater uniformity and strength of the electric field in the capacitor design. These results are appealing to widen the use of ion migration in technological applications such as neuromorphic computing or iontronics in general.     

Altered video task: a non-verbal measure of what-who-where recall in young children

This report aims to introduce, test and discuss a new method of measuring episodic memory in participants with highly restricted verbal abilities. Although an elicited/deferred imitation paradigm has already proposed a successful method of measuring this capacity in infants as young as 6 months old [Bauer, Patricia J. 2006. “Constructing a Past in Infancy: A Neuro-Developmental Account.” Trends in Cognitive Sciences 10 (4): 175–181], it failed to include a measure of capacities crucial for episodic recall, that is: a sense of self, a sense of subjective time and autonoetic consciousness [Tulving, Endel. 2002. “Episodic Memory: From Mind to Brain.” Annual Reviews Psychology 53: 1–25]. We combined developmental and comparative approaches in the altered video task to allow for simultaneous measuring of episodic recall and autonoetic consciousness. Episodic recall was measured via presentation of non-modified and modified recordings of a personal past event after a 24-h delay. The 15-month-old infants were expected to watch the modified video significantly longer than the non-modified video, and so evince the differentiation between them. Alongside, the infants participated in a mirror-mark task (a standard measure of self-recognition) and in a real-time video task (a possible alternative for the mirror-mark task). Results for ‘what’ and ‘who’ were consistent with our expectations. All results, their implications and possible future directions are discussed.     

VFO Path following Control with Guarantees of Positionally Constrained Transients for Unicycle-Like Robots with Constrained Control Input

The Vector-Field-Orientation (VFO) method is a control design concept which was originally introduced for the unicycle kinematics to solve two classical control tasks corresponding to the trajectory tracking and set-point control problems. A unified solution to both the tasks was possible by appropriate definitions of the so-called convergence vector field. So far, there has not been a version of the VFO control law for the third classical control task concerning the path following problem, which is particularly meaningful in the context of practical applications. The paper fills this gap by presenting a novel VFO path following controller devised for robots of unicycle-like kinematics with the amplitude-limited control input. Opposite to most path following controllers proposed in the literature, the new control law utilizes the recently introduced level curve approach which does not employ any parametrization of a reference path. In this way, the proposed solution is free of main limitations resulting from the need of unique determination of the shortest distance from a robot to the path. In contrast to other solutions, a formal analysis of the closed-loop dynamics presented in this paper provides sufficient conditions which guarantee constrained transients of robot motion with the position confined to a prescribed subset around a reference path. Theoretical results have been validated by numerical examples and experimentally verified with utilization of a laboratory-scale differentially driven robot.     

Multithreaded computing in evolutionary design and in artificial life simulations

This article investigates low-level and high-level multithreaded performance of evolutionary processes that are typically employed in evolutionary design and artificial life. Computations performed in these areas are specific because evaluation of each genotype usually involves time-consuming simulation of virtual environments and physics. Computational experiments have been conducted using the Framsticks simulator running a multithreaded version of a standard evolutionary experiment. Tests carried out on five diverse machines and two operating systems demonstrated how low-level performance depends on the number of physical and logical CPU cores and on the number of threads. Two string implementations have been compared, and their raw performance turned out to fundamentally differ in a multithreading setup. To improve high-level performance of parallel evolutionary algorithms, i.e. the quality of optimized solutions, a new distribution scheme that is especially useful and efficient for complex representations of solutions—the convection distribution—has been introduced. This new distribution scheme has been compared against a random distribution of genotypes among threads that carry out evolutionary processes.