3,485 research outputs found
Sy Montgomery and Matt Patterson: 2024 Cook Prize Gold Medal Winners
Author Sy Montgomery and illustrator Matt Patterson\u27s video for The Book of Turtles (Clarion)https://educate.bankstreet.edu/cook/1012/thumbnail.jp
Signaling through CD44 affects cell cycle progression and c-Jun expression in acute myeloid leukemia cells
We present here the first evidence linking CD44 signaling to c-Jun expression and cell cycle progression in myeloid cell line models. CD44 ligation with the anti-CD44 monoclonal antibodies have been shown to induce differentiation and inhibit the proliferation of human acute myeloid leukemia (AML) cells, and c-Jun is involved in the regulation of these processes. The effects of anti-CD44 monoclonal antibody A3D8, on myeloid cells were associated with specific disruption of cell cycle events and induction of G0/G1 arrest. Induction of G0/G1 arrest was accompanied by an increase in the expression of p21, attenuation of pRb phosphorylation and associated with decreased CDK2 and CDK4 kinase activities. We observed that A3D8 treatment of AML patient blasts and HL60/U937 cells led to the downregulation of c-Jun expression at mRNA and protein level. Transient transfection studies showed the inhibition of c-jun promoter activity by A3D8, involving both AP-1 sites. Furthermore, A3D8 treatment caused a decrease in JNK protein expression and a decrease in the level of phosphorylated c-Jun. Ectopic overexpression of c-Jun in HL60 cells was able to induce proliferation and prevent the anti-proliferative effects of A3D8. Targeting of G1 regulatory proteins and the resulting induction of G1 arrest by A3D8 may provide new insights into anti-proliferative and differentiation therapy of AML
Proto-oncogene c-jun expression is induced by AML1-ETO in a JNK dependent manner:possible role in the pathogenesis of acute myeloid leukemia
Overexpression of proto-oncogene c-jun and constitutive activation of the Jun NH2-terminal kinase (JNK) signaling pathway have been implicated in the leukemic transformation process. However, c-jun expression has not been investigated in acute myeloid leukemia (AML) cells containing the most common chromosomal translocations. t(8;21) is one of the most common AML-associated translocation and results in the AML1-ETO fusion protein. Overexpression of AML1-ETO in NIH3T3 cells leads to increased phosphorylation of Ser63 in c-Jun, which is generally JNK dependent. The role of the JNK signaling pathway for the functional properties of AML1-ETO is, however, unknown.
In the present study we found high expression levels of c-jun mRNA in t(8;21), t(15;17) or inv(16) positive patient cells by microarray analysis. Within t(8;21) positive patient samples, there was a correlation between AML1-ETO and c-jun mRNA expression levels. In myeloid U937 cells, c-jun mRNA and c-Jun protein expression levels increased upon induction of AML1-ETO. AML1-ETO transactivated the human c-jun promoter through the proximal AP-1 site via activating the JNK signaling pathway. JNK targets c-Jun and ATF-2, which also bind to the proximal AP-1 site in U937 cells, were also phosphorylated upon AML1-ETO induction. Furthermore, AML1-ETO induction increased the DNA binding capacity of c-Jun and ATF-2 to the proximal AP-1 site of the c-jun promoter, which might result in their enhanced transactivation capacities.
Interference with JNK and c-Jun activation by using JIP-1 or a JNK inhibitor reduced the transactivation capacity of AML1-ETO on the c-jun promoter and the pro-apoptotic function of AML1-ETO in U937 cells. AML1-ETO seems to activate the JNK signaling pathway by inducing the expression of a cytoplasmic factor, possibly G-CSF, because supernatant of AML1-ETO expressing cells was sufficient to induce phosphorylation of JNK and c-Jun in wildtype U937 cells.
This data demonstrates a novel mechanism of how AML1-ETO might exert positive effects on target gene expression and identifies the proto-oncogene c-jun as a common target gene in AML patient cells.Überexpression des Proto-Onkogens c-jun und konstitutive Aktivierung des Jun NH2-terminalen Kinase (JNK)-Signaltransduktionsweges sind wichtig für die leukämische Transformation in der Chronischen Myeloischen Leukämie. Die Expression von c-jun bei Akuter Myeloischer Leukämie (AML) mit den häufigsten reziproken Translokationen ist jedoch unbekannt. Bei einer der häufigsten AML Translokation t(8;21) wurde in Fibroblastenzellen gezeigt, daß das AML1-ETO-Fusionsgen die Phosphorylierung des Serin 63 in c-Jun erhöht. Die Rolle des JNK-Signalweges, der c-Jun am Serin 63 phosphorylieren kann, für die Funktion von AML1-ETO wurde bisher jedoch nicht untersucht. Weiterhin kann aktiviertes c-Jun durch eine positive Rückkoppelungsschleife über den c-jun Promotor zur Erhöhung der c-Jun Expression führen.
In der vorliegenden Arbeit konnten wir zeigen, daß AML Patientenzellen mit den häufigen Translokationen: t(8;21), t(15;17) oder inv(16) mehr c-jun mRNA besitzen im Vergleich zu Knochenmarkszellen gesunder Probanden. Weiterhin fanden wir eine hohe Korrelation zwischen der AML1-ETO und der c-jun mRNA bei t(8;21) positiven Patientenzellen. Induktion von AML1-ETO in der myeloischen U937 Zellinie erhöhte sowohl c-jun mRNA als auch c-Jun Proteinexpression. Damit konnten wir zeigen, daß AML1-ETO die Erhöhung der c-jun Expression bewirkt. Wir untersuchten den molekularen Mechanismus in U937 Zellen mittels transienter Transfektionen und fanden, daß AML1-ETO den c-jun Promotor durch die proximale AP-1 Seite transaktiviert. Diese Transaktivierung erfolgte indirekt über Aktivierung des JNK-Signaltransduktionsweges durch AML1-ETO. AML1-ETO-Induktion führte auch zur Phosphorylierung der JNK-Zielproteine c-Jun und ATF-2. Diese konnten im Gelretardierungsassay an die proximale AP-1 Seite des c-jun Promotors binden und wurden durch AML1-ETO-Induktion in ihrer Bindungsfähigkeit verstärkt. Deshalb nehmen wir an, daß die Transaktivierungskapazität des c-jun Promotors durch AML1-ETO über die Aktivierung des JNK-Signalweges läuft
Photometric study of a marginal contact binary SY Hor
32nd International Physics Congress of Turkish-Physical-Society (TPS) -- SEP 06-09, 2016 -- Bodrum, TURKEYIn this study, we present light curve analysis of a southern contact binary SY lior. Photometric parameters of the system and its components are derived using the Wilson and Devinney code based on the data taken from the SuperWASP public data archive. Photometric solutions indicate that SY Hai is a marginal contact binary system with a mass ratio of q = 1.59 and a contact degree of f = 6%.Turkish Phys So
Frequency insertion strategy for channel assignment problem
This paper presents a new heuristic method for quickly finding a good feasible solution to the channel assignment problem (CAP). Like many other greedy-type heuristics for CAP, the proposed method also assigns a frequency to a call, one at a time. Hence, the method requires computational time that increases only linear to the number of calls. However, what distinguishes the method from others is that it starts with a narrow enough frequency band so as to provoke violations of constraints that we need to comply with in order to avoid radio interference. Each violation is then resolved by inserting frequencies at the most appropriate positions so that the band of frequencies expands minimally. An extensive computational experiment using a set of randomly generated problems as well as the Philadelphia benchmark instances shows that the proposed method perform statistically better than existing methods of its kind and even yields optimum solutions to most of Philadelphia benchmark instances among which two cases are reported for the first time ever, in this paper.X113sciescopu
A Bayesian approach to prediction of system failure rates by criticalities under event trees
A Bayesian approach under a binary multi-stage event tree is proposed in estimating the system failure rate in various levels of criticality in order to incorporate failure data in one level into analyzing failure rates in any other levels. An initial failure which occurs according to a Poisson process with unknown rate is to escalate to more severe failures depending on functioning states of backup subsystems associated with the event tree. We employ the Gamma prior distribution for the initial failure rate and the Beta priors for the criticality probabilities. An approximation method is proposed to obtain the posterior distributions of the failure rates by criticalities. (C) 1999 Elsevier Science B.V. All rights reserved.X117sciescopu
A quasicontinuum method for deformations of carbon nanotubes
We present a coarse-graining computation for deformations of CNTs (carbon nanotubes) via QC (quasicontinuum), particularly targeting analysis of multi-waited carbon nanotubes. Higher order triangular elements are utilized for proper interpolation of atom positions of the CNT on the basis of QC approach. The computing scheme enables one to differentiate between the fully atomistic zone and the coarse-grained zone in the framework of the multiscale computing. Several numerical examples demonstrate the effectiveness and accuracy of the present methodology.This work was supported by the Ministry of Science and Technology of Korea through the National R&D Project for Nano Science and Technology (Grant no. M1-0213-04-0003). The authors would like to acknowledge the support from KISTI (Korea Institute of Science and Technology Information) under "the 6th Strategic Supercomputing Applications Support Program". The use of the computing system of the Supercomputing Center is also greatly appreciated
Optical evidence of amorphous-network change in the initial-growth stage a-Si : H
We investigated the optical characteristics of thin (<22 nm) hydrogenated amorphous silicon (a-Si:H) films by spectroscopic ellipsometry (SE). For comparison, we prepared H-2 diluted as well as undiluted a-Si:H samples on c-Si substrates. As the thickness decreases, the peak positions of dielectric functions (epsilon(r), epsilon(i)) Shifted to the higher-energy sides both in the H-2 diluted and the undiluted a-Si:H films. In addition, a noticeable difference of growth behavior between the H-2 diluted and the undiluted a-Si:H films was observed. To preclude effects caused by the incorporated hydrogens, the samples were annealed for sufficient dehydrogenation, which was verified by Fourier transform infrared spectroscopy (FTIR). Even after this dehydrogenation, there still remained a difference between the H-2 diluted and the undiluted samples, also, the evolution of the (epsilon(r), epsilon(i)) peak positions remained in the same relation as before the annealing. A simple chemical-alloy effect between silicon and hydrogen cannot explain these phenomena which may be a result of changes in the amorphous network. It is presumed that the structure of the amorphous network in the initial-growth stage is different from that of the amorphous network and the structure difference is enhanced by H-2 addition. (C) 2000 Elsevier Science B.V. All rights reserved
Atomistic simulations of incipient plasticity under A1(111) nanoindentation
Atomistic simulations are performed for the study of defect nucleation and evolution in A1 single crystal under nanoinclentation. Methodologies employed include the molecular dynamics and molecular mechanics simulations with embedded-atom potentials. Simulated is the indenting process on A1(111) surface with the spherical tip of indenter. Using the visualization technique of centrosymmetry parameters, homogeneous nucleations and early evolutions of dislocations are investigated for deepening our understanding of incipient plasticity at the atomic scale. We have shown that the nucleation sites of initial dislocation loops vary with the empirical potentials chosen for the simulation. Identifications are also made for the continuously changing structures of dislocation locks underneath the indenter tip and for the glide of prismatic partial dislocation loops far away from the contact surface. (c) 2005 Elsevier Ltd. All rights reserved
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