Interfacial motion in flexo- and order-electric switching between nematic filled states

We consider a nematic liquid crystal, in coexistence with its isotropic phase, in contact with a substrate patterned with rectangular grooves. In such a system, the nematic phase may fill the grooves without the occurrence of complete wetting. There may exist multiple (meta)stable filled states, each characterised by the type of distortion (bend or splay) in each corner of the groove and by the shape of the nematic-isotropic interface, and additionally the plateaux that separate the grooves may be either dry or wet with a thin layer of nematic. Using numerical simulations, we analyse the dynamical response of the system to an externally- applied electric field, with the aim of identifying switching transitions between these filled states. We find that order-electric coupling between the fluid and the field provides a means of switching between states where the plateaux between grooves are dry and states where they are wet by a nematic layer, without affecting the configuration of the nematic within the groove. We find that flexoelectric coupling may change the nematic texture in the groove, provided that the flexoelectric coupling differentiates between the types of distortion at the corners of the substrate. We identify intermediate stages of the transitions, and the role played by the motion of the nematic-isotropic interface. We determine quantitatively the field magnitudes and orientations required to effect each type of transition.Comment: 14 pages, 12 fig

Constraining the LRG Halo Occupation Distribution using Counts-in-Cylinders

The low number density of the Sloan Digital Sky Survey (SDSS) Luminous Red Galaxies (LRGs) suggests that LRGs occupying the same dark matter halo can be separated from pairs occupying distinct dark matter halos with high fidelity. We present a new technique, Counts-in-Cylinders (CiC), to constrain the parameters of the satellite contribution to the LRG Halo-Occupation Distribution (HOD). For a fiber collision-corrected SDSS spectroscopic LRG subsample at 0.16 < z < 0.36, we find the CiC multiplicity function is fit by a halo model where the average number of satellites in a halo of mass M is = ((M - Mcut)/M1)^alpha with Mcut = 5.0 +1.5/-1.3 (+2.9/-2.6) X 10^13 Msun, M1 = 4.95 +0.37/-0.26 (+0.79/-0.53) X 10^14 Msun, and alpha = 1.035 +0.10/-0.17 (+0.24/-0.31) at the 68% and 95% confidence levels using a WMAP3 cosmology and z=0.2 halo catalog. Our method tightly constrains the fraction of LRGs that are satellite galaxies, 6.36 +0.38/-0.39, and the combination Mcut/10^{14} Msun + alpha = 1.53 +0.08/-0.09 at the 95% confidence level. We also find that mocks based on a halo catalog produced by a spherical overdensity (SO) finder reproduce both the measured CiC multiplicity function and the projected correlation function, while mocks based on a Friends-of-Friends (FoF) halo catalog has a deficit of close pairs at ~1 Mpc/h separations. Because the CiC method relies on higher order statistics of close pairs, it is robust to the choice of halo finder. In a companion paper we will apply this technique to optimize Finger-of-God (FOG) compression to eliminate the 1-halo contribution to the LRG power spectrum.Comment: 40 pages, 9 figures, submitted to Astrophysical Journa

One-dimensional collision carts computer model and its design ideas for productive experiential learning

We develop an Easy Java Simulation (EJS) model for students to experience the physics of idealized one-dimensional collision carts. The physics model is described and simulated by both continuous dynamics and discrete transition during collision. In the field of designing computer simulations, we discuss briefly three pedagogical considerations such as 1) consistent simulation world view with pen paper representation, 2) data table, scientific graphs and symbolic mathematical representations for ease of data collection and multiple representational visualizations and 3) game for simple concept testing that can further support learning. We also suggest using physical world setup to be augmented complimentary with simulation while highlighting three advantages of real collision carts equipment like tacit 3D experience, random errors in measurement and conceptual significance of conservation of momentum applied to just before and after collision. General feedback from the students has been relatively positive, and we hope teachers will find the simulation useful in their own classes. 2015 Resources added: http://iwant2study.org/ospsg/index.php/interactive-resources/physics/02-newtonian-mechanics/02-dynamics/46-one-dimension-collision-js-model http://iwant2study.org/ospsg/index.php/interactive-resources/physics/02-newtonian-mechanics/02-dynamics/195-elastic-collisionComment: 6 pages, 8 figures, 1 table, 1 L. K. Wee, Physics Education 47 (3), 301 (2012); ISSN 0031-912

Macrophages in the Aging Liver and Age-Related Liver Disease

The number of individuals aged 65 or older is projected to increase globally from 524 million in 2010 to nearly 1. 5 billion in 2050. Aged individuals are particularly at risk for developing chronic illness, while being less able to regenerate healthy tissue and tolerate whole organ transplantation procedures. In the liver, these age-related diseases include non-alcoholic fatty liver disease, alcoholic liver disease, hepatitis, fibrosis, and cirrhosis. Hepatic macrophages, a population comprised of both Kupffer cells and infiltrating monocyte derived macrophages, are implicated in several chronic liver diseases and also play important roles in the homeostatic functions of the liver. The effects of aging on hepatic macrophage population dynamics, polarization, and function are not well understood. Studies performed on macrophages derived from other aged sources, such as the bone marrow, peritoneal cavity, lungs, and brain, demonstrate general reductions in autophagy and phagocytosis, dysfunction in cytokine signaling, and altered morphology and distribution, likely mediated by epigenetic changes and mitochondrial defects, that may be applicable to hepatic macrophages. This review highlights recent findings in macrophage developmental biology and function, particularly in the liver, and discusses the role of macrophages in various age-related liver diseases. A better understanding of the biology of aging that influences hepatic macrophages and thus the progression of chronic liver disease will be crucial in order to develop new interventions and treatments for liver disease in aging populations

Propranolol Sensitizes Vascular Sarcoma Cells to Doxorubicin by Altering Lysosomal Drug Sequestration and Drug Efflux

Angiosarcoma is a rare cancer of blood vessel–forming cells with a high patient mortality and few treatment options. Although chemotherapy often produces initial clinical responses, outcomes remain poor, largely due to the development of drug resistance. We previously identified a subset of doxorubicin-resistant cells in human angiosarcoma and canine hemangiosarcoma cell lines that exhibit high lysosomal accumulation of doxorubicin. Hydrophobic, weak base chemotherapeutics, like doxorubicin, are known to sequester within lysosomes, promoting resistance by limiting drug accessibility to cellular targets. Drug synergy between the beta adrenergic receptor (β-AR) antagonist, propranolol, and multiple chemotherapeutics has been documented in vitro, and clinical data have corroborated the increased therapeutic potential of propranolol with chemotherapy in angiosarcoma patients. Because propranolol is also a weak base and accumulates in lysosomes, we sought to determine whether propranolol enhanced doxorubicin cytotoxicity via antagonism of β-ARs or by preventing the lysosomal accumulation of doxorubicin. β-AR-like immunoreactivities were confirmed in primary tumor tissues and cell lines; receptor function was verified by monitoring downstream signaling pathways of β-ARs in response to receptor agonists and antagonists. Mechanistically, propranolol increased cytoplasmic doxorubicin concentrations in sarcoma cells by decreasing the lysosomal accumulation and cellular efflux of this chemotherapeutic agent. Equivalent concentrations of the receptor-active S-(−) and -inactive R-(+) enantiomers of propranolol produced similar effects, supporting a β-AR-independent mechanism. Long-term exposure of hemangiosarcoma cells to propranolol expanded both lysosomal size and number, yet cells remained sensitive to doxorubicin in the presence of propranolol. In contrast, removal of propranolol increased cellular resistance to doxorubicin, underscoring lysosomal doxorubicin sequestration as a key mechanism of resistance. Our results support the repurposing of the R-(+) enantiomer of propranolol with weak base chemotherapeutics to increase cytotoxicity and reduce the development of drug-resistant cell populations without the cardiovascular and other side effects associated with antagonism of β-ARs

Attention on Weak Ties in Social and Communication Networks

Granovetter's weak tie theory of social networks is built around two central hypotheses. The first states that strong social ties carry the large majority of interaction events; the second maintains that weak social ties, although less active, are often relevant for the exchange of especially important information (e.g., about potential new jobs in Granovetter's work). While several empirical studies have provided support for the first hypothesis, the second has been the object of far less scrutiny. A possible reason is that it involves notions relative to the nature and importance of the information that are hard to quantify and measure, especially in large scale studies. Here, we search for empirical validation of both Granovetter's hypotheses. We find clear empirical support for the first. We also provide empirical evidence and a quantitative interpretation for the second. We show that attention, measured as the fraction of interactions devoted to a particular social connection, is high on weak ties --- possibly reflecting the postulated informational purposes of such ties --- but also on very strong ties. Data from online social media and mobile communication reveal network-dependent mixtures of these two effects on the basis of a platform's typical usage. Our results establish a clear relationships between attention, importance, and strength of social links, and could lead to improved algorithms to prioritize social media content

Gravitational Waves from the Dynamical Bar Instability in a Rapidly Rotating Star

A rapidly rotating, axisymmetric star can be dynamically unstable to an m=2 "bar" mode that transforms the star from a disk shape to an elongated bar. The fate of such a bar-shaped star is uncertain. Some previous numerical studies indicate that the bar is short lived, lasting for only a few bar-rotation periods, while other studies suggest that the bar is relatively long lived. This paper contains the results of a numerical simulation of a rapidly rotating gamma=5/3 fluid star. The simulation shows that the bar shape is long lived: once the bar is established, the star retains this shape for more than 10 bar-rotation periods, through the end of the simulation. The results are consistent with the conjecture that a star will retain its bar shape indefinitely on a dynamical time scale, as long as its rotation rate exceeds the threshold for secular bar instability. The results are described in terms of a low density neutron star, but can be scaled to represent, for example, a burned-out stellar core that is prevented from complete collapse by centrifugal forces. Estimates for the gravitational-wave signal indicate that a dynamically unstable neutron star in our galaxy can be detected easily by the first generation of ground based gravitational-wave detectors. The signal for an unstable neutron star in the Virgo cluster might be seen by the planned advanced detectors. The Newtonian/quadrupole approximation is used throughout this work.Comment: Expanded version to be published in Phys. Rev. D: 13 pages, REVTeX, 13 figures, 9 TeX input file

Macrophage phenotype in response to ECM bioscaffolds

Macrophage presence and phenotype are critical determinants of the healing response following injury. Downregulation of the pro-inflammatory macrophage phenotype has been associated with the therapeutic use of bioscaffolds composed of extracellular matrix (ECM), but phenotypic characterization of macrophages has typically been limited to small number of non-specific cell surface markers or expressed proteins. The present study determined the response of both primary murine bone marrow derived macrophages (BMDM) and a transformed human mononuclear cell line (THP-1 cells) to degradation products of two different, commonly used ECM bioscaffolds; urinary bladder matrix (UBM-ECM) and small intestinal submucosa (SIS-ECM). Quantified cell responses included gene expression, protein expression, commonly used cell surface markers, and functional assays. Results showed that the phenotype elicited by ECM exposure (MECM) is distinct from both the classically activated IFNγ + LPS phenotype and the alternatively activated IL-4 phenotype. Furthermore, the BMDM and THP-1 macrophages responded differently to identical stimuli, and UBM-ECM and SIS-ECM bioscaffolds induced similar, yet distinct phenotypic profiles. The results of this study not only characterized an MECM phenotype that has anti-inflammatory traits but also showed the risks and challenges of making conclusions about the role of macrophage mediated events without consideration of the source of macrophages and the limitations of individual cell markers

Qatar-2: A K dwarf orbited by a transiting hot Jupiter and a more massive companion in an outer orbit

We report the discovery and initial characterization of Qatar-2b, a hot Jupiter transiting a V = 13.3 mag K dwarf in a circular orbit with a short period, P_ b = 1.34 days. The mass and radius of Qatar-2b are M_p = 2.49 M_j and R_p = 1.14 R_j, respectively. Radial-velocity monitoring of Qatar-2 over a span of 153 days revealed the presence of a second companion in an outer orbit. The Systemic Console yielded plausible orbits for the outer companion, with periods on the order of a year and a companion mass of at least several M_j. Thus Qatar-2 joins the short but growing list of systems with a transiting hot Jupiter and an outer companion with a much longer period. This system architecture is in sharp contrast to that found by Kepler for multi-transiting systems, which are dominated by objects smaller than Neptune, usually with tightly spaced orbits that must be nearly coplanar

Calmodulin-like proteins localized to the conoid regulate motility and cell invasion by Toxoplasma gondii

Toxoplasma gondii contains an expanded number of calmodulin (CaM)-like proteins whose functions are poorly understood. Using a combination of CRISPR/Cas9-mediated gene editing and a plant-like auxin-induced degron (AID) system, we examined the roles of three apically localized CaMs. CaM1 and CaM2 were individually dispensable, but loss of both resulted in a synthetic lethal phenotype. CaM3 was refractory to deletion, suggesting it is essential. Consistent with this prediction auxin-induced degradation of CaM3 blocked growth. Phenotypic analysis revealed that all three CaMs contribute to parasite motility, invasion, and egress from host cells, and that they act downstream of microneme and rhoptry secretion. Super-resolution microscopy localized all three CaMs to the conoid where they overlap with myosin H (MyoH), a motor protein that is required for invasion. Biotinylation using BirA fusions with the CaMs labeled a number of apical proteins including MyoH and its light chain MLC7, suggesting they may interact. Consistent with this hypothesis, disruption of MyoH led to degradation of CaM3, or redistribution of CaM1 and CaM2. Collectively, our findings suggest these CaMs may interact with MyoH to control motility and cell invasion