On secondary loops in LAOS via self-intersection of Lissajous–Bowditch curves

When the shear stress measured in large amplitude oscillatory shear (LAOS) deformation is represented as a 2-D Lissajous–Bowditch curve, the corresponding trajectory can appear to self-intersect and form secondary loops. This self-intersection is a general consequence of a strongly nonlinear material response to the imposed oscillatory forcing and can be observed for various material systems and constitutive models. We derive the mathematical criteria for the formation of secondary loops, quantify the location of the apparent intersection, and furthermore suggest a qualitative physical understanding for the associated nonlinear material behavior. We show that when secondary loops appear in the viscous projection of the stress response (the 2-D plot of stress vs. strain rate), they are best interpreted by understanding the corresponding elastic response (the 2-D projection of stress vs. strain). The analysis shows clearly that sufficiently strong elastic nonlinearity is required to observe secondary loops on the conjugate viscous projection. Such a strong elastic nonlinearity physically corresponds to a nonlinear viscoelastic shear stress overshoot in which existing stress is unloaded more quickly than new deformation is accumulated. This general understanding of secondary loops in LAOS flows can be applied to various molecular configurations and microstructures such as polymer solutions, polymer melts, soft glassy materials, and other structured fluids

Insights on the use of a-lipoic acid for therapeutic purposes

a-lipoic acid (ALA, thioctic acid) is an organosulfur component produced from plants, animals, and humans. It has various properties, among them great antioxidant potential and is widely used as a racemic drug for diabetic polyneuropathy-associated pain and paresthesia. Naturally, ALA is located in mitochondria, where it is used as a cofactor for pyruvate dehydrogenase (PDH) and a-ketoglutarate dehydrogenase complexes. Despite its various potentials, ALA therapeutic efficacy is relatively low due to its pharmacokinetic profile. Data suggests that ALA has a short half-life and bioavailability (about 30%) triggered by its hepatic degradation, reduced solubility as well as instability in the stomach. However, the use of various innovative formulations has greatly improved ALA bioavailability. The R enantiomer of ALA shows better pharmacokinetic parameters, including increased bioavailability as compared to its S enantiomer. Indeed, the use of amphiphilic matrices has capability to improve ALA bioavailability and intestinal absorption. Also, ALA’s liquid formulations are associated with greater plasma concentration and bioavailability as compared to its solidified dosage form. Thus, improved formulations can increase both ALA absorption and bioavailability, leading to a raise in therapeutic efficacy. Interestingly, ALA bioavailability will be dependent on age, while no difference has been found for gender. The present review aims to provide an updated on studies from preclinical to clinical trials assessing ALA’s usages in diabetic patients with neuropathy, obesity, central nervous system-related diseases and abnormalities in pregnancy.N. Martins would like to thank the Portuguese Foundation for Science and Technology (FCT-Portugal) for the Strategic project ref. UID/BIM/04293/2013 and “NORTE2020 - Northern Regional Operational Program” (NORTE-01-0145-FEDER-000012)

Alpha-N: Shortest Path Finder Automated Delivery Robot with Obstacle Detection and Avoiding System

Alpha N A self-powered, wheel driven Automated Delivery Robot is presented in this paper. The ADR is capable of navigating autonomously by detecting and avoiding objects or obstacles in its path. It uses a vector map of the path and calculates the shortest path by Grid Count Method of Dijkstra Algorithm. Landmark determination with Radio Frequency Identification tags are placed in the path for identification and verification of source and destination, and also for the recalibration of the current position. On the other hand, an Object Detection Module is built by Faster RCNN with VGGNet16 architecture for supporting path planning by detecting and recognizing obstacles. The Path Planning System is combined with the output of the GCM, the RFID Reading System and also by the binary results of ODM. This PPS requires a minimum speed of 200 RPM and 75 seconds duration for the robot to successfully relocate its position by reading an RFID tag. In the result analysis phase, the ODM exhibits an accuracy of 83.75 percent, RRS shows 92.3 percent accuracy and the PPS maintains an accuracy of 85.3 percent. Stacking all these 3 modules, the ADR is built, tested and validated which shows significant improvement in terms of performance and usability comparing with other service robots.Comment: 12 pages, 7 figures, To be appear in the proceedings of 12th Asian Conference on Intelligent Information and Database Systems 23-26 March 2020 Phuket, Thailan

Thrombosis Is Reduced by Inhibition of COX-1, but Unaffected by Inhibition of COX-2, in an Acute Model of Platelet Activation in the Mouse

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Regulatory subunits of PKA define an axis of cellular proliferation/differentiation in ovarian cancer cells

<p>Abstract</p> <p>Background</p> <p>The regulatory subunit of cAMP-dependent protein kinase (PKA) exists in two isoforms, RI and RII, which distinguish the PKA isozymes, type I (PKA-I) and type II (PKA-II). Evidence obtained from a variety of different experimental approaches has shown that the relative levels of type I and type II PKA in cells can play a major role in determining the balance between cell growth and differentiation. In order to characterize the effect of PKA type I and type II regulatory subunits on gene transcription at a global level, the PKA regulatory subunit genes for RIα and RIIβ were stably transfected into cells of the ovarian cancer cell line (OVCAR8).</p> <p>Results</p> <p>RIα transfected cells exhibit hyper-proliferative growth and RIIβ transfected cells revert to a relatively quiescent state. Profiling by microarray revealed equally profound changes in gene expression between RIα, RIIβ, and parental OVCAR cells. Genes specifically up-regulated in RIα cells were highly enriched for pathways involved in cell growth while genes up-regulated in RIIβ cells were enriched for pathways involved in differentiation. A large group of genes (~3600) was regulated along an axis of proliferation/differentiation between RIα, parental, and RIIβ cells. RIα/wt and RIIβ/wt gene regulation was shown by two separate and distinct gene set analytical methods to be strongly cross-correlated with a generic model of cellular differentiation.</p> <p>Conclusion</p> <p>Overexpression of PKA regulatory subunits in an ovarian cancer cell line dramatically influences the cell phenotype. The proliferation phenotype is strongly correlated with recently identified clinical biomarkers predictive of poor prognosis in ovarian cancer suggesting a possible pivotal role for PKA regulation in disease progression.</p

Enhanced electrochemical reduction of hydrogen peroxide by Co3O4 nanowire electrode

Crystalline Co3O4 nanowire arrays with different morphologies grown on Ni foam were investigated by varying the reaction temperature, the concentration of precursors, and reaction time. The Co3O4 nanowires synthesized under typical reaction condition had a diameter range of approximately 500–900 nm with a length of 17 µm. Electrochemical reduction of hydrogen peroxide (H2O2) of the optimized Co3O4 nanowire electrode was studied by cyclic voltammetry. A high current density of 101.8 mA cm−2 was obtained at −0.4 V in a solution of 0.4 M H2O2 and 3.0 M NaOH at room temperature compared to 85.8 mA cm−2 at −0.35 V of the Co3O4 nanoparticle electrode. Results clearly indicated that the Ni foam supported Co3O4 nanowire electrode exhibited superior catalytic activity and mass transport kinetics for H2O2 electrochemical reduction

MicroRNA-34a modulates genes involved in cellular motility and oxidative phosphorylation in neural precursors derived from human umbilical cord mesenchymal stem cells

<p>Abstract</p> <p>Background</p> <p>Mesenchymal stem cell (MSC) found in bone marrow (BM-MSCs) and the Wharton's jelly matrix of human umbilical cord (WJ-MSCs) are able to transdifferentiate into neuronal lineage cells both <it>in vitro </it>and <it>in vivo </it>and therefore hold the potential to treat neural disorders such as stroke or Parkinson's disease. In bone marrow MSCs, miR-130a and miR-206 have been show to regulate the synthesis of neurotransmitter substance P in human mesenchymal stem cell-derived neuronal cells. However, how neuronal differentiation is controlled in WJ-MSC remains unclear.</p> <p>Methods</p> <p>WJ-MSCs were isolated from human umbilical cords. We subjected WJ-MSCs into neurogenesis by a published protocol, and the miRNome patterns of WJ-MSCs and their neuronal progenitors (day 9 after differentiation) were analyzed by the Agilent microRNA microarray.</p> <p>Results</p> <p>Five miRNAs were enriched in WJ-MSCs, including miR-345, miR-106a, miR-17-5p, miR-20a and miR-20b. Another 11 miRNAs (miR-206, miR-34a, miR-374, miR-424, miR-100, miR-101, miR-323, miR-368, miR-137, miR-138 and miR-377) were abundantly expressed in transdifferentiated neuronal progenitors. Among these miRNAs, miR-34a and miR-206 were the only 2 miRNAs been linked to BM-MSC neurogenesis. Overexpressing miR-34a in cells suppressed the expression of 136 neuronal progenitor genes, which all possess putative miR-34a binding sites. Gene enrichment analysis according to the Gene Ontology database showed that those 136 genes were associated with cell motility, energy production (including those with oxidative phosphorylation, electron transport and ATP synthesis) and actin cytoskeleton organization, indicating that miR-34a plays a critical role in precursor cell migration. Knocking down endogenous miR-34a expression in WJ-MSCs resulted in the augment of WJ-MSC motility.</p> <p>Conclusions</p> <p>Our data suggest a critical role of miRNAs in MSC neuronal differentiation, and miR-34a contributes in neuronal precursor motility, which may be crucial for stem cells to home to the target sites they should be.</p

Expression of the RNA helicase DDX3 and the hypoxia response in breast cancer

&lt;p&gt;Aims: DDX3 is an RNA helicase that has antiapoptotic properties, and promotes proliferation and transformation. In addition, DDX3 was shown to be a direct downstream target of HIF-1α (the master regulatory of the hypoxia response) in breast cancer cell lines. However, the relation between DDX3 and hypoxia has not been addressed in human tumors. In this paper, we studied the relation between DDX3 and the hypoxic responsive proteins in human breast cancer.&lt;/p&gt; &lt;p&gt;Methods and Results: DDX3 expression was investigated by immunohistochemistry in breast cancer in comparison with hypoxia related proteins HIF-1α, GLUT1, CAIX, EGFR, HER2, Akt1, FOXO4, p53, ERα, COMMD1, FER kinase, PIN1, E-cadherin, p21, p27, Transferrin receptor, FOXO3A, c-Met and Notch1. DDX3 was overexpressed in 127 of 366 breast cancer patients, and was correlated with overexpression of HIF-1α and its downstream genes CAIX and GLUT1. Moreover, DDX3 expression correlated with hypoxia-related proteins EGFR, HER2, FOXO4, ERα and c-Met in a HIF-1α dependent fashion, and with COMMD1, FER kinase, Akt1, E-cadherin, TfR and FOXO3A independent of HIF-1α.&lt;/p&gt; &lt;p&gt;Conclusions: In invasive breast cancer, expression of DDX3 was correlated with overexpression of HIF-1α and many other hypoxia related proteins, pointing to a distinct role for DDX3 under hypoxic conditions and supporting the oncogenic role of DDX3 which could have clinical implication for current development of DDX3 inhibitors.&lt;/p&gt

Platelets generated from human embryonic stem cells are functional in vitro and in the microcirculation of living mice

Platelets play an essential role in hemostasis and atherothrombosis. Owing to their short storage time, there is constant demand for this life-saving blood component. In this study, we report that it is feasible to generate functional megakaryocytes and platelets from human embryonic stem cells (hESCs) on a large scale. Differential-interference contrast and electron microscopy analyses showed that ultrastructural and morphological features of hESC-derived platelets were indistinguishable from those of normal blood platelets. In functional assays, hESC-derived platelets responded to thrombin stimulation, formed microaggregates, and facilitated clot formation/retraction in vitro. Live cell microscopy demonstrated that hESC-platelets formed lamellipodia and filopodia in response to thrombin activation, and tethered to each other as observed in normal blood. Using real-time intravital imaging with high-speed video microscopy, we have also shown that hESC-derived platelets contribute to developing thrombi at sites of laser-induced vascular injury in mice, providing the first evidence for in vivo functionality of hESC-derived platelets. These results represent an important step toward generating an unlimited supply of platelets for transfusion. Since platelets contain no genetic material, they are ideal candidates for early clinical translation involving human pluripotent stem cells