Basins of attraction in forced systems with time-varying dissipation

We consider dissipative periodically forced systems and investigate cases in which having information as to how the system behaves for constant dissipation may be used when dissipation varies in time before settling at a constant final value. First, we consider situations where one is interested in the basins of attraction for damping coefficients varying linearly between two given values over many different time intervals: we outline a method to reduce the computation time required to estimate numerically the relative areas of the basins and discuss its range of applicability. Second, we observe that sometimes very slight changes in the time interval may produce abrupt large variations in the relative areas of the basins of attraction of the surviving attractors: we show how comparing the contracted phase space at a time after the final value of dissipation has been reached with the basins of attraction corresponding to that value of constant dissipation can explain the presence of such variations. Both procedures are illustrated by application to a pendulum with periodically oscillating support.Comment: 16 pages, 13 figures, 7 table

The Transcriptome of Human Endometrial Mesenchymal Stem Cells Under TGFβR Inhibition Reveals Improved Potential for Cell-Based Therapies

Mesenchymal stem/stromal cells (MSCs) are multipotent cells with favorable properties for cell therapies and regenerative medicine. Human endometrium harbors a small population of perivascular, clonogenic MSCs (eMSCs) identified by the SUSD2 marker. As for other MSCs, eMSCs require extensive in vitro expansion to generate clinically relevant numbers of cells, resulting in spontaneous differentiation, replicative senescence and cell death, decreasing therapeutic potency. We previously demonstrated that A83-01, a TGF-β receptor inhibitor, maintained eMSC clonogenicity, promoted proliferation, prevented apoptosis and maintained MSC function in vitro. Here we compare the transcriptome of passaged eMSCs from six women cultured with and without A83-01 for 7 days. We identified 1206 differentially expressed genes (DEG) using a false discovery rate cut-off at 0.01 and fold change >2. Significant enrichment of genes involved in anti-inflammatory responses, angiogenesis, cell migration and proliferation, and collagen fibril and extracellular matrix organization were revealed. TGF-β, Wnt and Akt signaling pathways were decreased. Anti-fibrotic and anti-apoptotic genes were induced, and fibroblast proliferation and myofibroblast related genes were downregulated. We found increased MSC potency genes (TWIST1, TWIST2, JAG1, LIFR, and SLIT2) validating the enhanced potency of A83-01-treated eMSCs, and importantly no pluripotency gene expression. We also identified eMSCs’ potential for secreting exosomes, possibly explaining their paracrine properties. Angiogenic and cytokine protein arrays confirmed the angiogenic, anti-fibrotic and immunomodulatory phenotype of A83-01-treated eMSCs, and increased angiogenic activity was functionally demonstrated in vitro. eMSCs culture expanded with A83-01 have enhanced clinically relevant properties, suggesting their potential for cell-therapies and regenerative medicine applications

Reflection of underwater sound from surface waves

Author Posting. © Acoustical Society of America, 2009. This article is posted here by permission of Acoustical Society of America for personal use, not for redistribution. The definitive version was published in Journal of the Acoustical Society of America 125 (2009): 66-72, doi:10.1121/1.3035828.A tank experiment has been conducted to measure reflection of underwater sound from surface waves. Reflection from a wave crest leads to focusing and caustics and results in rapid variation in the received waveform as the surface wave moves. Theoretical results from wavefront modeling show that interference of three surface reflected eigenrays for each wave crest produces complicated interference waveforms. There is good agreement between theory and experiment even on the shadow side of caustics where there are two surface reflected arrivals but only one eigenray.The support of the Office of Naval Research, Grant No. N00014-04-1-0728, is gratefully acknowledge

Impact of oxygen levels on human hematopoietic stem and progenitor cell expansion

Oxygen levels are an important variable during the in vitro culture of stem cells. There has been increasing interest in the use of low oxygen to maximize proliferation and, in some cases, effect differentiation of stem cell populations. It is generally assumed that the defined pO2 in the incubator reflects the pO2 to which the stem cells are being exposed. However, we demonstrate that the pO2 experienced by cells in static culture can change dramatically during the course of culture as cell numbers increase and as the oxygen utilization by cells exceeds the diffusion of oxygen through the media. Dynamic culture (whereby the cell culture plate is in constant motion) largely eliminates this effect, and a combination of low ambient oxygen and dynamic culture results in a fourfold increase in reconstituting capacity of human hematopoietic stem cells compared with those cultured in static culture at ambient oxygen tension. Cells cultured dynamically at 5% oxygen exhibited the best expansion: 30-fold increase by flow cytometry, 120-fold increase by colony assay, and 11% of human CD45 engraftment in the bone marrow of NOD/SCID mice. To our knowledge, this is the first study to compare individual and combined effects of oxygen and static or dynamic culture on hematopoietic ex vivo expansion. Understanding and controlling the effective oxygen tension experienced by cells may be important in clinical stem cell expansion systems, and these results may have relevance to the interpretation of low oxygen culture studies

Manual / Issue 12 / On Further Review

Manual, a journal about art and its making. On Further Review. This issue uncovers narratives once central to objects’ histories but that now have been systematically obscured, inadvertently overlooked, or otherwise lost. Softcover, 96 pages. Published 2019 by the RISD Museum.(On Further Review) contributors include Anita N. Bateman, Laurie Anne Brewer, Becci Davis, Jamie Gabbarelli, Bethany Johns, Elon Cook Lee, Kevin McBride, Walker Mettling, Jessica Rosner, Suzanne Scanlan, Nell Painter, Allison Pappas, Pamela A. Parmal, Shiyanthi Thavapalan, and Nick White.https://digitalcommons.risd.edu/risdmuseum_journals/1038/thumbnail.jp

A Road Map for the Exploration of Neighboring Planetary Systems (ExNPS)

A brown dwarf star having only 20-50 times the mass of Jupiter is located below and to the left of the bright star GL 229 in this image from the Hubble Space Telescope. At the 19 light year distance to GL 229, the 7.7-arcsec separation between the star and the brown dwarf corresponds to roughly the separation between Pluto and the Sun in our Solar System. The goal of the program described in this report is to detect and characterize Earth-like planets around nearby stars where conditions suitable for life might be found. For a star like the Sun located 30 light years away, the appropriate star-planet separation would be almost 100 times closer than seen here for GL 229B

The role of resveratrol on skeletal muscle cell differentiation and myotube hypertrophy during glucose restriction

Glucose restriction (GR) impairs muscle cell differentiation and evokes myotube atrophy. Resveratrol treatment in skeletal muscle cells improves inflammatory-induced reductions in skeletal muscle cell differentiation. We therefore hypothesised that resveratrol treatment would improve muscle cell differentiation and myotube hypertrophy in differentiating C2C12 myoblasts and mature myotubes during GR. Glucose restriction at 0.6 g/L (3.3 mM) blocked differentiation and myotube hypertrophy versus high-glucose (4.5 g/L or 25 mM) differentiation media (DM) conditions universally used for myoblast culture. Resveratrol (10 μM) treatment increased SIRT1 phosphorylation in DM conditions, yet did not improve differentiation when administered to differentiating myoblasts in GR conditions. Resveratrol did evoke increases in hypertrophy of mature myotubes under DM conditions with corresponding elevated Igf-I and Myhc7 gene expression, coding for the ‘slow’ type I MYHC protein isoform. Inhibition of SIRT1 via EX-527 administration (100 nM) also reduced myotube diameter and area in DM conditions and resulted in lower gene expression of Myhc 1, 2 and 4 coding for ‘intermediate’ and ‘faster’ IIx, IIa and IIb protein isoforms, respectively. Resveratrol treatment did not appear to modulate phosphorylation of energy-sensing protein AMPK or protein translation initiator P70S6K. Importantly, in mature myotubes, resveratrol treatment was able to ameliorate reduced myotube growth in GR conditions over an acute 24-h period, but not over 48–72 h. Overall, resveratrol evoked myotube hypertrophy in DM conditions while favouring ‘slower’ Myhc gene expression and acutely ameliorated impaired myotube growth observed during glucose restriction

Ten Simple Rules for Effective Computational Research

<p>Ten Simple Rules for Effective Computational Research</p

Disruption of arterial perivascular drainage of amyloid-β from the brains of mice expressing the human APOE ε4 allele

Failure of elimination of amyloid-β (Aβ) from the brain and vasculature appears to be a key factor in the etiology of sporadic Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA). In addition to age, possession of an apolipoprotein E (APOE) ε4 allele is a strong risk factor for the development of sporadic AD. The present study tested the hypothesis that possession of the APOE ε4 allele is associated with disruption of perivascular drainage of Aβ from the brain and with changes in cerebrovascular basement membrane protein levels. Targeted replacement (TR) mice expressing the human APOE3 (TRE3) or APOE4 (TRE4) genes and wildtype mice received intracerebral injections of human Aβ40. Aβ40 aggregated in peri-arterial drainage pathways in TRE4 mice, but not in TRE3 or wildtype mice. The number of Aβ deposits was significantly higher in the hippocampi of TRE4 mice than in the TRE3 mice, at both 3- and 16-months of age, suggesting that clearance of Aβ was disrupted in the brains of TRE4 mice. Immunocytochemical and Western blot analysis of vascular basement membrane proteins demonstrated significantly raised levels of collagen IV in 3-month-old TRE4 mice compared with TRE3 and wild type mice. In 16-month-old mice, collagen IV and laminin levels were unchanged between wild type and TRE3 mice, but were lower in TRE4 mice. The results of this study suggest that APOE4 may increase the risk for AD through disruption and impedance of perivascular drainage of soluble Aβ from the brain. This effect may be mediated, in part, by changes in age-related expression of basement membrane proteins in the cerebral vasculature