Development and pathologies of the arterial wall

Arteries consist of an inner single layer of endothelial cells surrounded by layers of smooth muscle and an outer adventitia. The majority of vascular developmental studies focus on the construction of endothelial networks through the process of angiogenesis. Although many devastating vascular diseases involve abnormalities in components of the smooth muscle and adventitia (i.e., the vascular wall), the morphogenesis of these layers has received relatively less attention. Here, we briefly review key elements underlying endothelial layer formation and then focus on vascular wall development, specifically on smooth muscle cell origins and differentiation, patterning of the vascular wall, and the role of extracellular matrix and adventitial progenitor cells. Finally, we discuss select human diseases characterized by marked vascular wall abnormalities. We propose that continuing to apply approaches from developmental biology to the study of vascular disease will stimulate important advancements in elucidating disease mechanism and devising novel therapeutic strategies.     

Sonochemical synthesis of nanostructured nickel hydroxide as an electrode material for improved electrochemical energy storage application

A facile and fast approach for the synthesis of a nanostructured nickel hydroxide(Ni(OH)_2) via sonochemical technique is reported in the present study. The X-ray diffraction results confirmed that the synthesized Ni(OH)_2 was oriented in β-phase of hexagonal brucite structure. The nanostructured Ni(OH)_2 electrode exhibited the maximum specific capacitance of 1256 F/g at a current density of 200 mA/g in 1 M KOH_((aq)). Ni(OH)_2 electrodes exhibited the pseudocapacitive behavior due to the presence of redox reaction. It also exhibited long-term cyclic stability of 85% after 2000 cycles, suggesting that the nanostructured Ni(OH)_2 electrode will play a promising role for high performance supercapacitor application.     

Social Media as a Mean for Improved Technical Communication

Technical communication (TC) is an important activity in order to provide the users of technical artifacts with necessary information concerning the operation and maintenance of the products they are using. In the current working procedures of TC, however, the users become too passive. They are just receivers of information. Further, there is no effective feedback from the users to the producers of the information. In order to overcome those problems we here propose an application of social media (SM) in future TC. By using SM as a complementary channel for TC it becomes possible for technology firms to boost their competitive advantage and to improve the quality and completeness of their TC. This technique, however, is still more of a potential and less of a reality. Several problems, mostly concerning security and confidentiality remain to be solved. The empirical base for this work comes from TIC, an EU-funded development project involving several Swedish technology companies. Published research results are somewhat scattered but several sources coherently indicate both the need and potential for SM as a vehicle in TC. By scanning the net it is further possible to identify a number of seemingly successful applications of SM in such applications.     

The concept of intelligibility in modern physics (1948)

This is an English translation of Paul Feyerabend's earliest extant essay “Der Begriff der Verständlichkeit in der modernen Physik” (1948). In it, Feyerabend defends positivism as a progressive framework for scientific research in certain stages of scientific development. He argues that in physics visualizability (Anschaulichkeit) and intelligibility (Verständlichkeit) are time-conditioned concepts: what is deemed visualizable in the development of physical theories is relative to a specific historical context and changes over time. He concludes that from time to time the abandonment of visualizability is crucial for progress in physics, as it is conducive to major theory change, illustrating the point on the basis of advances in atomic theory.     

Tyrosine 842 in the activation loop is required for full transformation by the oncogenic mutant FLT3-ITD

The type III receptor tyrosine kinase FLT3 is frequently mutated in acute myeloid leukemia. Oncogenic FLT3 mutants display constitutive activity leading to aberrant cell proliferation and survival. Phosphorylation on several critical tyrosine residues is known to be essential for FLT3 signaling. Among these tyrosine residues, Y842 is located in the so-called activation loop. The position of this tyrosine residue is well conserved in all receptor tyrosine kinases. It has been reported that phosphorylation of the activation loop tyrosine is critical for catalytic activity for some but not all receptor tyrosine kinases. The role of Y842 residue in FLT3 signaling has not yet been studied. In this report, we show that Y842 is not important for FLT3 activation or ubiquitination but plays a critical role in regulating signaling downstream of the receptor as well as controlling receptor stability. We found that mutation of Y842 in the FLT3-ITD oncogenic mutant background reduced cell viability and increased apoptosis. Furthermore, the introduction of the Y842 mutation in the FLT3-ITD background led to a dramatic reduction in in vitro colony forming capacity. Additionally, mice injected with cells expressing FLT3-ITD/Y842F displayed a significant delay in tumor formation, compared to FLT3-ITD expressing cells. Microarray analysis comparing gene expression regulated by FLT3-ITD versus FLT3-ITD/Y842F demonstrated that mutation of Y842 causes suppression of anti-apoptotic genes. Furthermore, we showed that cells expressing FLT3-ITD/Y842F display impaired activity of the RAS/ERK pathway due to reduced interaction between FLT3 and SHP2 leading to reduced SHP2 activation. Thus, we suggest that Y842 is critical for FLT3-mediated RAS/ERK signaling and cellular transformation.     

Phospholipid flippases attenuate LPS-induced TLR4 signaling by mediating endocytic retrieval of Toll-like receptor 4

P4-ATPases are lipid flippases that catalyze the transport of phospholipids to create membrane phospholipid asymmetry and to initiate the biogenesis of transport vesicles. Here we show, for the first time, that lipid flippases are essential to dampen the inflammatory response and to mediate the endotoxin-induced endocytic retrieval of Toll-like receptor 4 (TLR4) in human macrophages. Depletion of CDC50A, the β-subunit that is crucial for the activity of multiple P4-ATPases, resulted in endotoxin-induced hypersecretion of proinflammatory cytokines, enhanced MAP kinase signaling and constitutive NF-κB activation. In addition, CDC50A-depleted THP-1 macrophages displayed reduced tolerance to endotoxin. Moreover, endotoxin-induced internalization of TLR4 was strongly reduced and coincided with impaired endosomal MyD88-independent signaling. The phenotype of CDC50A-depleted cells was also induced by separate knockdown of two P4-ATPases, namely ATP8B1 and ATP11A. We conclude that lipid flippases are novel elements of the innate immune response that are essential to attenuate the inflammatory response, possibly by mediating endotoxin-induced internalization of TLR4.     

ARFIMA approximation and forecasting of the limiting aggregate structure of long‐memory process

This article studies Man and Tiao's (2006) low‐order autoregressive fractionally integrated moving‐average (ARFIMA) approximation to Tsai and Chan's (2005b) limiting aggregate structure of the long‐memory process. In matching the autocorrelations, we demonstrate that the approximation works well, especially for larger d values. In computing autocorrelations over long lags for larger d value, using the exact formula one might encounter numerical problems. The use of the ARFIMA(0, d, d?₁) model provides a useful alternative to compute the autocorrelations as a really close approximation. In forecasting future aggregates, we demonstrate the close performance of using the ARFIMA(0, d, d?₁) model and the exact aggregate structure. In practice, this provides a justification for the use of a low‐order ARFIMA model in predicting future aggregates of long‐memory process. Copyright © 2008 John Wiley & Sons, Ltd.