“…Phosphorylated FAK on serine 732 localized at the microtubules of the spindle and contributed to microtubule dynamics and mitosis control [30]. Lamin B is essential for cell viability [20], and down-regulating lamin B1 in HeLa cells caused apoptosis [31]. Lower lamin B1 expression in FAK-inhibited SMMC-7721 cells might be related to cell apoptosis.…”
Section: Discussionmentioning
confidence: 98%
“…Furthermore, lamins help to control the exchange between nucleus and cytoplasm [20]. Lamin B1 is the type V intermediate filament protein and has been implicated in cancers.…”
Section: Depletion Of Fak Reduced Lamin B1 Expressionmentioning
Focal adhesion kinase (FAK) plays important roles in cancer development. However, the significance of FAK expression in colorectal carcinoma and hepatocellular carcinoma has not been clarified. This study aims to explore the roles FAK played in the progression of colorectal carcinoma and hepatocellular carcinoma. RNAi method was used to inhibit the expression of FAK in Caco2 and SMMC-7721 cells. Reverse transcriptase polymerase chain reaction analysis and Western blot analysis were used to examine mRNA and protein expression of FAK. Then, the proliferation, motility and apoptosis of both types of cells were detected using MTT assay, wound healing/transwell assay and nuclear staining assay. The microstructure changes (F-actin, β-tubulin and lamin B1) of SMMC-7721 cells were visualized by immunofluorescence. FAK was overexpressed in both cell lines and down-regulation of FAK resulted in suppression of cell proliferation, inhibition of cell migration and invasion. The apoptosis of cells was increased significantly following the FAK expression inhibition. Moreover, actin polymerization, β-tubulin and lamin B1 expression of cells were significantly decreased. The results highlight the role of FAK in the progression of cancers. These findings suggest FAK serve as a potential therapeutic target for cancer therapy.
“…Phosphorylated FAK on serine 732 localized at the microtubules of the spindle and contributed to microtubule dynamics and mitosis control [30]. Lamin B is essential for cell viability [20], and down-regulating lamin B1 in HeLa cells caused apoptosis [31]. Lower lamin B1 expression in FAK-inhibited SMMC-7721 cells might be related to cell apoptosis.…”
Section: Discussionmentioning
confidence: 98%
“…Furthermore, lamins help to control the exchange between nucleus and cytoplasm [20]. Lamin B1 is the type V intermediate filament protein and has been implicated in cancers.…”
Section: Depletion Of Fak Reduced Lamin B1 Expressionmentioning
Focal adhesion kinase (FAK) plays important roles in cancer development. However, the significance of FAK expression in colorectal carcinoma and hepatocellular carcinoma has not been clarified. This study aims to explore the roles FAK played in the progression of colorectal carcinoma and hepatocellular carcinoma. RNAi method was used to inhibit the expression of FAK in Caco2 and SMMC-7721 cells. Reverse transcriptase polymerase chain reaction analysis and Western blot analysis were used to examine mRNA and protein expression of FAK. Then, the proliferation, motility and apoptosis of both types of cells were detected using MTT assay, wound healing/transwell assay and nuclear staining assay. The microstructure changes (F-actin, β-tubulin and lamin B1) of SMMC-7721 cells were visualized by immunofluorescence. FAK was overexpressed in both cell lines and down-regulation of FAK resulted in suppression of cell proliferation, inhibition of cell migration and invasion. The apoptosis of cells was increased significantly following the FAK expression inhibition. Moreover, actin polymerization, β-tubulin and lamin B1 expression of cells were significantly decreased. The results highlight the role of FAK in the progression of cancers. These findings suggest FAK serve as a potential therapeutic target for cancer therapy.
“…98 Price stability as a legal requirement, not to mention a constitutional one, was off the table; various attempts to stretch the law in this direction failed. 99 Only the monetary turmoil of the 1970s brought Klasen and his successor Emminger to shift to inflation targeting. 100 Even then they pursued that path for political rather than economic reasons.…”
Section: The Constitutionalization Of Moneymentioning
This article argues that the PSPP judgment effectively buries the era of financial liberalism, which has dominated the European economic constitution for decades. It raises the curtain on a new political paradigm, which I call “integrative liberalism”. Whereas the financial crisis put financial liberalism under strain, the development since then has been contradictory, torn between state intervention and market liberalism, focused above all on buying time rather than finding a new constitutional equilibrium. Now, together with the measures adopted in response to COVID-19, the PSPP judgment paves the way for profound change. Integrative liberalism is characterized by an overall shift from the market to the state, mitigating the post-crisis insistence on austerity and conditionality. Contrary to the embedded liberalism of the post-war era, integrative liberalism operates in a corrective and reactive mode with a focus on goals and principles, lacking the emphasis on long-term planning. Like every political paradigm, integrative liberalism ushers in a new understanding of the law. It puts the emphasis on context instead of discipline, and it elevates the proportionality principle. If integrative liberalism is to succeed, however, the democratic legitimacy of the Eurosystem and its independence require serious reconsideration.
“…Altogether, the key property of epigenetic data is that while the raw data is reported at nucleotide resolution nearby Implementation Availability Probability Distribution Data Format Supported Method class CROCS (14) Yes Gaussian, Poisson, Negative Binomial ChIP-seq Breakpoint detection with structured constraints (originally proposed as gfpop (18)). PELT (12) Yes Flexible Flexible Break-point detection with pruned dynamical programming Yokoyama et al (23) No Binomial WGBS Application of PELT Herrmann et al (8) No Binomial ( signal vs. input) ChIP-seq Bayesian MCMC Chen et al (2) No Gaussian ChIP-seq Bayesian MCMC Xing et al (22) No Poisson ChIP-seq Hidden-markov model chromosomal positions are likely to be produced by the same biological or experimental process and this fact can be exploited to define narrow peaks, broad peaks, or DMRs. While these analysis approaches are popular and effective, they rely on specific assumptions, tunable parameters, or, in the case of DMRs, on knowledge of experimental design.…”
Motivation: Epigenetic assays using next-generation sequencing (NGS) have furthered our understanding of the functional genomic regions and the mechanisms of gene regulation. However, a single assay produces billions of data represented by nucleotide resolution signal tracks. The signal strength at a given nucleotide is subject to numerous sources of technical a biological noise and thus conveys limited information about the underlying biological state. In order to draw biological conclusions, data is typically summarized into higher order patterns. Numerous specialized algorithms for summarizing epigenetic signal have been proposed and include methods for peak calling or finding differentially methylated regions. A key unifying principle underlying these approaches is that they all leverage the strong prior that signal must be locally consistent. Results: We propose L0 segmentation as a universal framework for extracting locally coherent signals for diverse epigenetic sources. L0 serves to both compress and smooth the input signal by approximating it as piece-wise constant. We implement a highly scalable L0 segmentation with additional loss functions designed for NGS epigenetic data types including Poisson loss for single tracks and binomial loss for methylation/coverage data. In contrast to the widely used L1 segmentation problem, known as fused lasso, the L0 solution does not induce global attenuation and is able to capture the salient features of the data over a wide range of compression values. Finally, we show that L0 segmentation can be used as an effective prior inside other machine learning models, such as matrix factorization.
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