73 research outputs found
Quasiperiodic Tip Splitting in Directional Solidification
We report experimental results on the tip splitting dynamics of seaweed
growth in directional solidification of succinonitrile alloys with
poly(ethylene oxide) or acetone as solutes. The seaweed or dense branching
morphology was selected by solidifying grains which are oriented close to the
{111} plane. Despite the random appearance of the growth, a quasiperiodic tip
splitting morphology was observed in which the tip alternately splits to the
left and to the right. The tip splitting frequency f was found to be related to
the growth velocity V as a power law f V^{1.5}. This finding
is consistent with the predictions of a tip splitting model that is also
presented. Small anisotropies are shown to lead to different kinds of seaweed
morphologies.Comment: 4 pages, 7 figures, submitted to Physical Review Letter
The relation of steady evaporating drops fed by an influx and freely evaporating drops
We discuss a thin film evolution equation for a wetting evaporating liquid on
a smooth solid substrate. The model is valid for slowly evaporating small
sessile droplets when thermal effects are insignificant, while wettability and
capillarity play a major role. The model is first employed to study steady
evaporating drops that are fed locally through the substrate. An asymptotic
analysis focuses on the precursor film and the transition region towards the
bulk drop and a numerical continuation of steady drops determines their fully
non-linear profiles.
Following this, we study the time evolution of freely evaporating drops
without influx for several initial drop shapes. As a result we find that drops
initially spread if their initial contact angle is larger than the apparent
contact angle of large steady evaporating drops with influx. Otherwise they
recede right from the beginning
Lubricating Bacteria Model for Branching growth of Bacterial Colonies
Various bacterial strains (e.g. strains belonging to the genera Bacillus,
Paenibacillus, Serratia and Salmonella) exhibit colonial branching patterns
during growth on poor semi-solid substrates. These patterns reflect the
bacterial cooperative self-organization. Central part of the cooperation is the
collective formation of lubricant on top of the agar which enables the bacteria
to swim. Hence it provides the colony means to advance towards the food. One
method of modeling the colonial development is via coupled reaction-diffusion
equations which describe the time evolution of the bacterial density and the
concentrations of the relevant chemical fields. This idea has been pursued by a
number of groups. Here we present an additional model which specifically
includes an evolution equation for the lubricant excreted by the bacteria. We
show that when the diffusion of the fluid is governed by nonlinear diffusion
coefficient branching patterns evolves. We study the effect of the rates of
emission and decomposition of the lubricant fluid on the observed patterns. The
results are compared with experimental observations. We also include fields of
chemotactic agents and food chemotaxis and conclude that these features are
needed in order to explain the observations.Comment: 1 latex file, 16 jpeg files, submitted to Phys. Rev.
Carcinogenic Effects in a Phenylketonuria Mouse Model
Phenylketonuria (PKU) is a metabolic disorder caused by impaired phenylalanine hydroxylase (PAH). This condition results in hyperphenylalaninemia and elevated levels of abnormal phenylalanine metabolites, among which is phenylacetic acid/phenylacetate (PA). In recent years, PA and its analogs were found to have anticancer activity against a variety of malignancies suggesting the possibility that PKU may offer protection against cancer through chronically elevated levels of PA. We tested this hypothesis in a genetic mouse model of PKU (PAHenu2) which has a biochemical profile that closely resembles that of human PKU. Plasma levels of phenylalanine in homozygous (HMZ) PAHenu2 mice were >12-fold those of heterozygous (HTZ) littermates while tyrosine levels were reduced. Phenylketones, including PA, were also markedly elevated to the range seen in the human disease. Mice were subjected to 7,12 dimethylbenz[a]anthracene (DMBA) carcinogenesis, a model which is sensitive to the anticancer effects of the PA derivative 4-chlorophenylacetate (4-CPA). Tumor induction by DMBA was not significantly different between the HTZ and HMZ mice, either in total tumor development or in the type of cancers that arose. HMZ mice were then treated with 4-CPA as positive controls for the anticancer effects of PA and to evaluate its possible effects on phenylalanine metabolism in PKU mice. 4-CPA had no effect on the plasma concentrations of phenylalanine, phenylketones, or tyrosine. Surprisingly, the HMZ mice treated with 4-CPA developed an unexplained neuromuscular syndrome which precluded its use in these animals as an anticancer agent. Together, these studies support the use of PAHenu2 mice as a model for studying human PKU. Chronically elevated levels of PA in the PAHenu2 mice were not protective against cancer
Synergistic inhibition of prostate cancer cell lines by a 19- nor hexafluoride vitamin D3 analogue and anti-activator protein 1 retinoid
The secosteroid hormones, all- trans- and 9- cis -retinoic acid and vitamin D3, have demonstrated significant capacity to control proliferation in itro of many solid tumour cell lines. Cooperative synergistic effects by these two ligands have been reported, and it is, therefore, possible that greater therapeutic effects could be achieved if these compounds were administered together. The role of retinoid-dependent anti-activator protein 1 (anti-AP-1) effects in controlling cancer cell proliferation appears significant. We have utilized an anti- AP-1 retinoid [2-(4,4-dimethyl-3,4-dihydro-2H-1 benzopyran-6-yl)carbonyl-2-(4-carboxyphenyl)-1,3,-dithiane; SR11238], which does not transactivate through a retinoic acid response element (RARE), and a potent vitamin D3analogue [1Ξ±,25(OH)2-16-ene-23-yne-26,27-F6-19-nor -D3, code name LH] together at low, physiologically safer doses against a panel of prostate cancer cell lines that represent progressively more transformed phenotypes. The LNCaP (least transformed) and PC-3 (intermediately transformed) cell lines were synergistically inhibited in their clonal growth by the combination of LH and SR11238, whereas SR11238 alone was essentially inactive. DU-145 cells (most transformed) were completely insensitive to these analogues. LNCaP cells, but neither PC-3 nor DU-145, underwent apoptosis in the presence of LH and SR11238. Transactivation of the human osteocalcin vitamin D response element (VDRE) by LH was not enhanced in the presence of SR11238, although the expression of E-cadherin in these cells was additively up-regulated in the presence of both compounds. These data suggest the anti-AP-1 retinoid and the vitamin D3 analogue may naturally act synergistically to control cell proliferation, a process that is interrupted during transformation, and that this combination may form the basis for treatment of some androgen-independent prostate cancer. Β© 1999 Cancer Research Campaig
Complementary effects of HDAC inhibitor 4-PB on gap junction communication and cellular export mechanisms support restoration of chemosensitivity of PDAC cells
Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease and one of the cancer entities with the lowest life expectancy. Beside surgical therapy, no effective therapeutic options are available yet. Here, we show that 4-phenylbutyrate (4-PB), a known and well-tolerable inhibitor of histone deacetylases (HDAC), induces up to 70% apoptosis in all cell lines tested (Panc 1, T4M-4, COLO 357, BxPc3). In contrast, it leads to cell cycle arrest in only half of the cell lines tested. This drug increases gap junction communication between adjacent T3M-4 cells in a concentration-dependent manner and efficiently inhibits cellular export mechanisms in Panc 1, T4M-4, COLO 357 and BxPc3 cells. Consequently, in combination with gemcitabine 4-PB shows an overadditive effect on induction of apoptosis in BxPc3 and T3M-4 cells (up to 4.5-fold compared to single drug treatment) with accompanied activation of Caspase 8, BH3 interacting domain death agonist (Bid) and poly (ADP-ribose) polymerase family, member 1 (PARP) cleavage. Although the inhibition of the mitogen-activated protein kinase-pathway has no influence on fulminant induction of apoptosis, the inhibition of the JNK-pathway by SP600125 completely abolishes the overadditive effect induced by the combined application of both drugs, firstly reported by this study
MicroRNA and mRNA profiling in the idiopathic inflammatory myopathies
Background The idiopathic inflammatory myopathies (IIMs) are heterogeneous autoimmune conditions of skeletal muscle inflammation and weakness. MicroRNAs (miRNAs) are short, non-coding RNA which regulate gene expression of target mRNAs. The aim of this study was to profile miRNA and mRNA in IIM and identify miRNA-mRNA relationships which may be relevant to disease. Methods mRNA and miRNA in whole blood samples from 7 polymyositis (PM), 7 dermatomyositis (DM), 5 inclusion body myositis and 5 non-myositis controls was profiled using next generation RNA sequencing. Gene ontology and pathway analyses were performed using GOseq and Ingenuity Pathway Analysis. Dysregulation of miRNAs and opposite dysregulation of predicted target mRNAs in IIM subgroups was validated using RTqPCR and investigated by transfecting human skeletal muscle cells with miRNA mimic. Results Analysis of differentially expressed genes showed that interferon signalling, and anti-viral response pathways were upregulated in PM and DM compared to controls. An anti-Jo1 autoantibody positive subset of PM and DM (n =β5) had more significant upregulation and predicted activation of interferon signalling and highlighted T-helper (Th1 and Th2) cell pathways. In miRNA profiling miR-96-5p was significantly upregulated in PM, DM and the anti-Jo1 positive subset. RTqPCR replicated miR-96-5p upregulation and predicted mRNA target (ADK, CD28 and SLC4A10) downregulation. Transfection of a human skeletal muscle cell line with miR-96-5p mimic resulted in significant downregulation of ADK. Conclusion MiRNA and mRNA profiling identified dysregulation of interferon signalling, anti-viral response and T-helper cell pathways, and indicates a possible role for miR-96-5p regulation of ADK in pathogenesis of IIM
Induction of erythroid differentiation and fetal hemoglobin production in human leukemic cells treated with phenylacetate
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