50,279 research outputs found
C-Jun N-terminal kinases/c-Jun and p38 pathways cooperate in ceramide-induced neuronal apoptosis
No full textUnderstanding the regulation of the apoptotic program in neurons by intracellular pathways is currently a subject of great interest. Recent results suggest that c-Jun N-terminal kinases (JNK), mitogen-activated protein kinases and the transcription factor c-Jun are important regulators of this cell death program in post-mitotic neurons following survival-factor withdrawal. Our study demonstrates that ceramide levels increase upon survival-factor withdrawal in primary cultured cortical neurons. Furthermore, survival-factor withdrawal or addition of exogenous c2-ceramide induces JNK pathway activation in these cells. Western blot analyses of JNK and c-Jun using phospho-specific antibodies reveal that JNK and subsequent c-Jun phosphorylation occur hours before the initiation of apoptosis, reflected morphologically by neurite retraction and fragmentation, cell-body shrinkage and chromatin fragmentation. Immunocytochemistry using the same antibodies shows that phospho-JNK are localized in the neurites of control neurons and translocate to the nucleus where phospho-c-Jun concurrently appears upon ceramide-induced apoptosis. To determine if ceramide-induced c-Jun activation is responsible for the induction of the apoptotic program, we performed transient transfections of a dominant negative form of c-Jun, truncated in its transactivation region. Our results show that DNc-Jun partially protects cortical neurons from ceramide-induced apoptosis. Treatment of dominant negative c-Jun-expressing neurons with the pharmacological inhibitor of p38 kinase, SB203580, completely blocked neuronal death. Thus our data show that p38 and JNK/c-Jun pathways cooperate to induce neuronal apoptosis
Dataset for Studying Cross-Session Variability in Motor Imagery Brain-Computer Interface
No full textThis is a code script used to verify SHU Dataverse.
The researcher will download the dataset first, and save all the files of the dataset in ./or_data/
Proto-oncogene c-jun expression is induced by AML1-ETO in a JNK dependent manner:possible role in the pathogenesis of acute myeloid leukemia
No full textOverexpression 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
The k-support norm and convex envelopes of cardinality and rank
No full textSparsity, or cardinality, as a tool for feature selection is extremely common in a vast number of current computer vision applications. The k-support norm is a recently proposed norm with the proven property of providing the tightest convex bound on cardinality over the Euclidean norm unit ball. In this paper we present a re-derivation of this norm, with the hope of shedding further light on this particular surrogate function. In addition, we also present a connection between the rank operator, the nuclear norm and the k-support norm. Finally, based on the results established in this re-derivation, we propose a novel algorithm with significantly improved computational efficiency, empirically validated on a number of different problems, using both synthetic and real world data.Anders Eriksson, Trung Thanh Pham, Tat-Jun Chin, Ian Rei
Xizang feng ma qi yi shu
No full textBen shu yi tu wen bing mao de xing shi dui feng ma qi yi shu jin xing le jiao quan mian de jie shao. gai shu zhu yao jie shao feng ma qi de qi yuan, feng ma qi de han yi feng ma qi de xing zhuang he zhong lei yi ji feng ma qi yi shu de te se he feng g
Efficient globally optimal consensus maximisation with tree search
No full textMaximum consensus is one of the most popular criteria for robust estimation in computer vision. Despite its widespread use, optimising the criterion is still customarily done by randomised sample-and-test techniques, which do not guarantee optimality of the result. Several globally optimal algorithms exist, but they are too slow to challenge the dominance of randomised methods. We aim to change this state of affairs by proposing a very efficient algorithm for global maximisation of consensus. Under the framework of LP-type methods, we show how consensus maximisation for a wide variety of vision tasks can be posed as a tree search problem. This insight leads to a novel algorithm based on A* search. We propose efficient heuristic and support set updating routines that enable A* search to rapidly find globally optimal results. On common estimation problems, our algorithm is several orders of magnitude faster than previous exact methods. Our work identifies a promising solution for globally optimal consensus maximisation.Tat-Jun Chin, Pulak Purkait, Anders Eriksson, and David Sute
A non-gaussian continuous state space model for asset degradation
No full textThe degradation model plays an essential role in asset life prediction and condition based maintenance. Various degradation models have been proposed. Within these models, the state space model has the ability to combine degradation data and failure event data. The state space model is also an effective approach to deal with the multiple observations and missing data issues. Using the state space degradation model, the deterioration process of assets is presented by a system state process which can be revealed by a sequence of observations. Current research largely assumes that the underlying system development process is discrete in time or states. Although some models have been developed to consider continuous time and space, these state space models are based on the Wiener process with the Gaussian assumption. This paper proposes a Gamma-based state space degradation model in order to remove the Gaussian assumption. Both condition monitoring observations and failure events are considered in the model so as to improve the accuracy of asset life prediction. A simulation study is carried out to illustrate the application procedure of the proposed model
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