The influence of thrombopoietin (TpO) on human erythropoiesis. In vitro studies--clinical implications

beta-Glucuronidase of human or bacterial origin may deconjugate bilirubin diglucuronide, causing pigment gallstones. Intrinsic interference by biliary compounds must be minimized for accurate assay of beta-glucuronidase. We report a modified ion-pair extraction of interfering substances by tetrahexylammonium chloride (THAC) in ethyl acetate in the presence of albumin, and a microtitre plate assay for biliary beta-glucuronidase activity in bile with the substrate p-nitrophenol-glucuronide. Adding albumin improved the recovery of beta-glucuronidase activity to 99.8% (CV 1.9%), and 92.2% of the bilirubin in bile samples was extracted in one step. Competitive inhibition was overcome by increasing the substrate concentration. In endoscopically obtained common duct bile from 44 patients, five different beta-glucuronidase activity peaks were identified, at pH 3.9, 4.8, 5.3, 5.8 and 7.2. The pH profiles were classified into one bacterial pattern and five patterns for presumed human beta-glucuronidase. Of the latter patterns, four displayed dual activity peaks. In a second sample, obtained at follow up in four patients, their original pH profile was maintained. In conclusion, using the modified purification and assay system, we found functionally diverse subcategories of human beta-glucuronidase with respect to activity at variable pH. Our results indicate that several pH optima have to be taken into consideration in order to clarify the role of human biliary beta-glucuronidase in the pathogenesis of pigment gallstones. Bacterial beta-glucuronidase activity was associated with duodenal diverticula (p < 0.05) and common duct stones (p < 0.05).     

The role of insulin (INS) and insulin-like growth factor-I (IGF-I) in regulating human erythropoiesis. Studies in vitro under serum-free conditions--comparison to other cytokines and growth factors

The role of insulin (INS), and insulin-like growth factor-I (IGF-I) in the regulation of human erythropoiesis is not completely understood. To address this issue we employed several complementary strategies including: serum free cloning of CD34+ cells, RT-PCR, FACS analysis, and mRNA perturbation with oligodeoxynucleotides (ODN). In a serum-free culture model, both INS and IGF-I enhanced survival of CD34+ cells, but neither of these growth factors stimulated their proliferation. The influence of INS and IGF-I on erythroid colony development was dependent on a combination of growth factors used for stimulating BFU-E growth. When BFU-E growth was optimally stimulated with erythropoietin (EpO) + kit ligand (KL) the large erythroid colonies developed normally even in the absence of INS or IGF-I. However, the addition of both of these growth factors slightly enhanced colony size. On the other hand, if erythroid colonies were stimulated suboptimally with EpO + IL-3 only, INS or IGF-I increased the number of small erythroid bursts by approximately 30%. Both INS and IGF-I activated signal transduction in maturing human erythropoietic cells as determined by phosphorylation of the insulin receptor substrate-2 (IRS-2) protein. We also found by RT-PCR that mRNA coding for INS-R is expressed in FACS sorted CD34+, c-kit-R+ marrow cells, and in cells isolated from BFU-E and CFU-GM colonies. Expression of INS-R protein on these cells was subsequently confirmed by cytofluorometry. In contrast, the receptor for insulin-like growth factor-I (IGF-IR) was not detected on CD34+ cells, and was first easily detectable on more differentiated cells derived from day 6 BFU-E and CFU-GM colonies. We conclude that INS and IGF-I may be survival factors for human CD34+ cells, but are not required during early erythropoiesis. In contrast, both growth factors may play some role at the final stages of erythroid maturation.     

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.     

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.     

Projection‐based model reduction for contact problems

To be feasible for computationally intensive applications such as parametric studies, optimization, and control design, large‐scale finite element analysis requires model order reduction. This is particularly true in nonlinear settings that tend to dramatically increase computational complexity. Although significant progress has been achieved in the development of computational approaches for the reduction of nonlinear computational mechanics models, addressing the issue of contact remains a major hurdle. To this effect, this paper introduces a projection‐based model reduction approach for both static and dynamic contact problems. It features the application of a non‐negative matrix factorization scheme to the construction of a positive reduced‐order basis for the contact forces, and a greedy sampling algorithm coupled with an error indicator for achieving robustness with respect to model parameter variations. The proposed approach is successfully demonstrated for the reduction of several two‐dimensional, simple, but representative contact and self contact computational models. Copyright © 2015 John Wiley & Sons, Ltd.