The DTExtm method allows simultaneous analysis of changes in gene expression levels of 145 ADME-associated genes using a microarray. Total RNA is converted to cDNA and labeled before being hybridized to the DTExtm microarray. The method can survey basal gene expression levels and coordinated changes in expression levels caused by drug treatment in various cell lines and tissues. Rifampicin treatment of human hepatocytes showed induction of genes such as CYP3A4, UGT1A1, and ABCB1 in a coordinated manner mediated by PXR activation. Benzoflavone treatment also coordinately induced CYP1A2, UGT1A1, and ABCC2 through AHR activation. DTE
The document discusses how AP-2α induces apoptosis in cancer cells. It finds that AP-2α activates the intrinsic apoptosis pathway by binding to the Bcl-2 promoter and repressing its transcription. This allows Bax to translocate to mitochondria, disrupt membrane potential, and release cytochrome c, activating caspase-9 and caspase-3. Downregulation of anti-apoptotic Bcl-2 is important for AP-2α-induced apoptosis. Overexpressing AP-2α enhances cancer cell chemosensitivity to various drugs.
BioROIS Co., Ltd is a Japanese venture company established in 2006 to commercialize bio-related technologies developed at the National Institute of Genetics. The company developed the Auxin Inducible Degron (AID) system, which allows for rapid degradation of target proteins in mammalian cells through the addition of auxin. The AID system allows target proteins to be degraded within 30 minutes, much faster than other gene expression control systems. BioROIS licenses the AID system technology and sells AID system kits to support life science research.
Role of FXR and other nuclear receptors in liver fibrosis - Prof Stefano Fior...Attività scientifica
1) The nuclear receptor FXR is expressed in hepatocytes and hepatic stellate cells (HSCs).
2) Activation of FXR in HSCs inhibits their activation and transdifferentiation into myofibroblasts by reducing the expression of fibrotic markers.
3) The antifibrotic effects of FXR in HSCs are partly mediated by the induction of the atypical nuclear receptor SHP, which represses the expression of genes involved in bile acid synthesis and fibrogenesis.
1) The nuclear receptor FXR is expressed in hepatic stellate cells and its activation reduces stellate cell proliferation and the expression of fibrotic markers.
2) FXR activation induces the expression of SHP, which inhibits stellate cell activation and collagen production.
3) FXR ligands have shown antifibrotic effects in animal models of liver fibrosis by modulating stellate cell function and cross-talking with other nuclear receptors like PPARγ.
1) The study evaluated the effects of two growth hormone receptor (GHR) mutations (p.R229H and c.899dupC) found in a patient with GH insensitivity.
2) Functional studies showed that the p.R229H mutation did not impair GHR signaling or function. However, the c.899dupC mutation resulted in a truncated GHR protein that was unable to activate downstream signaling pathways in response to GH.
3) When coexpressed, the c.899dupC mutation dominantly inhibited the normal signaling of wild-type GHR and the p.R229H variant. This dominant negative effect explains the patient's GH insensitivity phenotype.
The document describes the establishment of immortalized human amniotic epithelial cell (iHAE) lines. HAE cells were extracted from placentas and infected with retroviruses containing HPV16 E6/E7 and hTERT genes to extend their lifespan. The iHAE lines showed extended proliferation ability and expression of stem cell markers. They maintained multipotent differentiation potential as demonstrated by their ability to differentiate into adipocytes, osteocytes, neurons, and cardiac cell types. The iHAE cells represent a promising new cell source for applications in regenerative medicine and cell therapy due to their immunosuppressive properties and differentiation potential.
The document describes using peptidomics to monitor protease inhibition in vivo by analyzing peptides as surrogates for protease activity. Peptidomics allows the comprehensive analysis of endogenous peptides from biological samples. The study demonstrates inhibiting different proteases in rats, including DPPIV and FXA, and analyzing changes in peptide levels. Several novel protease substrates were identified, including an ITM2B peptide for DPPIV. Collagen peptide levels were also strongly affected by DPPIV inhibition, indicating its importance in collagen metabolism. Peptidomics can thus non-invasively monitor protease activity and inhibition in vivo by analyzing surrogate peptide markers.
Control of liver fibrosis by nuclear receptors - Prof Stefano FiorucciAttività scientifica
The document discusses the role of nuclear receptors in controlling liver fibrosis. It describes several nuclear receptors expressed in hepatic stellate cells, including PPARβ/γ, PXR, FXR, and SHP. Activation of these receptors reduces stellate cell proliferation and the expression of fibrotic markers. Studies show that ligands for PPARγ, FXR, and PXR decrease liver fibrosis in rodent models by inducing a phenotypic switch in stellate cells from an activated to quiescent state.
The document discusses how AP-2α induces apoptosis in cancer cells. It finds that AP-2α activates the intrinsic apoptosis pathway by binding to the Bcl-2 promoter and repressing its transcription. This allows Bax to translocate to mitochondria, disrupt membrane potential, and release cytochrome c, activating caspase-9 and caspase-3. Downregulation of anti-apoptotic Bcl-2 is important for AP-2α-induced apoptosis. Overexpressing AP-2α enhances cancer cell chemosensitivity to various drugs.
BioROIS Co., Ltd is a Japanese venture company established in 2006 to commercialize bio-related technologies developed at the National Institute of Genetics. The company developed the Auxin Inducible Degron (AID) system, which allows for rapid degradation of target proteins in mammalian cells through the addition of auxin. The AID system allows target proteins to be degraded within 30 minutes, much faster than other gene expression control systems. BioROIS licenses the AID system technology and sells AID system kits to support life science research.
Role of FXR and other nuclear receptors in liver fibrosis - Prof Stefano Fior...Attività scientifica
1) The nuclear receptor FXR is expressed in hepatocytes and hepatic stellate cells (HSCs).
2) Activation of FXR in HSCs inhibits their activation and transdifferentiation into myofibroblasts by reducing the expression of fibrotic markers.
3) The antifibrotic effects of FXR in HSCs are partly mediated by the induction of the atypical nuclear receptor SHP, which represses the expression of genes involved in bile acid synthesis and fibrogenesis.
1) The nuclear receptor FXR is expressed in hepatic stellate cells and its activation reduces stellate cell proliferation and the expression of fibrotic markers.
2) FXR activation induces the expression of SHP, which inhibits stellate cell activation and collagen production.
3) FXR ligands have shown antifibrotic effects in animal models of liver fibrosis by modulating stellate cell function and cross-talking with other nuclear receptors like PPARγ.
1) The study evaluated the effects of two growth hormone receptor (GHR) mutations (p.R229H and c.899dupC) found in a patient with GH insensitivity.
2) Functional studies showed that the p.R229H mutation did not impair GHR signaling or function. However, the c.899dupC mutation resulted in a truncated GHR protein that was unable to activate downstream signaling pathways in response to GH.
3) When coexpressed, the c.899dupC mutation dominantly inhibited the normal signaling of wild-type GHR and the p.R229H variant. This dominant negative effect explains the patient's GH insensitivity phenotype.
The document describes the establishment of immortalized human amniotic epithelial cell (iHAE) lines. HAE cells were extracted from placentas and infected with retroviruses containing HPV16 E6/E7 and hTERT genes to extend their lifespan. The iHAE lines showed extended proliferation ability and expression of stem cell markers. They maintained multipotent differentiation potential as demonstrated by their ability to differentiate into adipocytes, osteocytes, neurons, and cardiac cell types. The iHAE cells represent a promising new cell source for applications in regenerative medicine and cell therapy due to their immunosuppressive properties and differentiation potential.
The document describes using peptidomics to monitor protease inhibition in vivo by analyzing peptides as surrogates for protease activity. Peptidomics allows the comprehensive analysis of endogenous peptides from biological samples. The study demonstrates inhibiting different proteases in rats, including DPPIV and FXA, and analyzing changes in peptide levels. Several novel protease substrates were identified, including an ITM2B peptide for DPPIV. Collagen peptide levels were also strongly affected by DPPIV inhibition, indicating its importance in collagen metabolism. Peptidomics can thus non-invasively monitor protease activity and inhibition in vivo by analyzing surrogate peptide markers.
Control of liver fibrosis by nuclear receptors - Prof Stefano FiorucciAttività scientifica
The document discusses the role of nuclear receptors in controlling liver fibrosis. It describes several nuclear receptors expressed in hepatic stellate cells, including PPARβ/γ, PXR, FXR, and SHP. Activation of these receptors reduces stellate cell proliferation and the expression of fibrotic markers. Studies show that ligands for PPARγ, FXR, and PXR decrease liver fibrosis in rodent models by inducing a phenotypic switch in stellate cells from an activated to quiescent state.
A reading report for <A Secreted Slit2 Fragment Regulates Adipose Tissue Ther...星云 王
A reading report for <A Secreted Slit2 Fragment Regulates Adipose Tissue Thermogenesis and Metabolic Function
>, only for private study use, please do not use it for profit or public.
Fiorucci presents research on the role of bile acids and their activation of nuclear receptors such as FXR in regulating gastrointestinal mucosa integrity. Bile acids are endogenous ligands for FXR and other receptors that modulate inflammation. Activation of FXR was shown to reduce markers of colitis and inflammation in mouse models of inflammatory bowel disease. FXR deficient mice had increased inflammation and tissue damage compared to controls in response to colitis induction. Pharmacological FXR activation also reduced inflammation. This suggests FXR plays an important role in innate immunity and protection of the GI tract from inflammation.
Discriminating Facts from Artefacts in the Secreted Ly-6 Protein FamilyChris Southan
The document discusses several issues related to accurately characterizing the secreted Ly-6 protein family based on bioinformatic analysis. It describes the discovery of novel rat Ly-6 proteins from urine samples and EST data, but also finds chimeric mRNA sequences that combined portions of unrelated genes with Ly-6 sequences, complicating the analysis. Genome mapping showed the chimeras did not represent real gene fusions but likely arose from artifacts. While many rat and mouse homologs were identified, clear orthologs between species were difficult to determine due to high sequence divergence over time.
The document describes research into identifying potent inhibitors of the SHP2 protein tyrosine phosphatase. Several small molecule inhibitors were discovered, including NSC-87877, which was shown to selectively inhibit SHP2 activity in vitro and in cell-based assays. It was the first evidence that SHP2 phosphatase is involved in growth factor-stimulated ERK activation. Further screening of a chemical library identified additional SHP2 inhibitors, such as HLM002903 and HLM019544, which were shown to inhibit SHP2-dependent cell growth and signaling. The goal of finding SHP2 inhibitors is to develop potential anti-cancer agents, as SHP2 mutations have been implicated in various cancers and
1. The document discusses various pathways and receptors involved in bile acid metabolism and signaling, including the farnesoid X receptor (FXR).
2. It shows that glycyrrhizic acid, a component of licorice, is a potent FXR agonist in vitro.
3. Administration of glycyrrhizic acid was found to activate FXR signaling and protect against aspirin-induced gastric lesions in mice by increasing prostaglandin levels.
The document describes assays to demonstrate the mechanism of action of SXN101959, a targeted secretion inhibitor being developed for the treatment of acromegaly. It outlines cellular and in vivo assays to show that SXN101959 binds and activates growth hormone-releasing hormone receptors, is internalized into cells, cleaves SNARE proteins via its enzymatic domain, and inhibits pulsatile growth hormone secretion. A battery of assays using receptor expressing cell lines and pituicytes aims to validate the mechanism of action at each step in multiple preclinical species.
This document summarizes a study that analyzed the frequency of the CYP4F2 rs2108622 genetic variant among 90 healthy Jordanian volunteers. The study found:
- The frequency of the C allele was 0.55 and of the T allele was 0.45.
- The most common genotype was heterozygous CT at 0.55 frequency.
- The frequencies in Jordanians were similar to Caucasians but different from other groups like Africans.
- This variant may influence cardiovascular diseases and warfarin response in Jordanians.
This research project studied post-translational modifications (PTMs) of nicotinamide phosphoribosyltransferase (NAMPT) through site-directed mutagenesis. NAMPT is the rate-limiting enzyme in the NAD+ salvage pathway. The document details the cloning of NAMPT cDNA into expression vectors, generation of point mutations at various PTM sites, expression and purification of mutant proteins, and initial analysis. Future work will involve further mutagenesis and characterization of the mutated NAMPT proteins to better understand how PTMs regulate NAMPT activity and NAD+ regeneration.
Senior Thesis-Analyzing the interactions between MYOGEF and a component of er...Dougan McGrath
This document summarizes a study analyzing the interaction between MYOGEF, a guanine nucleotide exchange factor that activates RhoA, and SPTA1, a major component of the erythrocyte cytoskeleton. Previous research identified SPTA1 as an interacting partner of MYOGEF. The current study aims to characterize this interaction through constructing cDNA fragments of different regions of MYOGEF and SPTA1 and examining their interaction using yeast two-hybrid and in vitro pull-down assays. The results showed that the C-terminal region of MYOGEF interacted with the EF-hand motifs located in the C-terminal region of SPTA1. This interaction may lead to MYOGEF-mediated
The DIONESUS algorithm provides a scalable and accurate method to reconstruct dynamic phosphoproteomic networks and reveal new drug targets. The document describes an experiment where the DIONESUS algorithm was applied to phosphorylation kinetics data from panels of growth factors, small molecule inhibitors, and antioxidants tested on A431 cells. Inhibition of SRC family kinases or PLCγ pathways attenuated EGF-stimulated cell death, while inhibition of PI3K, autocrine signaling pathways, or antioxidants decreased cell viability. The phosphorylation profiles informed dynamic network modeling to infer signaling pathways and potential drug targets.
2014 lecture next generation metabolic screening - Marrakech Ron Wevers
Next Generation Metabolic Screening is a novel technique that can be applied to body fluids as urine, plasma or cerebrospinal fluid for the diagnosis of inborn errors of metabolism. The technique gives a holistic view on metabolism (metabolomics) and uses LC_Qtof mass spectrometry. The technique was developed in Nijmegen, The Netherlands in the group of Prof Ron Wevers (ron.wevers@radboudumc.nl)
The document describes research sequencing the human lymph peptidome using various mass spectrometry techniques. Over 900 peptides were identified from over 480 proteins. The peptides came from intracellular, extracellular, and membrane proteins. Some peptides bound strongly to MHC II molecules, indicating they could be immunologically relevant. Analysis of the molecular functions and pathways identified acute phase response and coagulation proteins. Protease processing pathways generating the peptidome involved matrix metalloproteases, cathepsins, and enzymes from innate immunity and coagulation. The study provides new insights into self-antigens and peptides presented by immune cells.
SuperScript IV Reverse Transcriptase for RNA Analysis | ESHG 2015 Poster PS14...Thermo Fisher Scientific
Survey and interview studies conducted over a three year period revealed that researchers are not satisfied with their current reverse transcriptase and are performing reactions with increasingly difficult samples, such as poorly purified RNA and unpurified RNA (direct RT) that both contain inhibitors. To meet this performance gap, the Thermo Fisher Life Sciences Solutions group produced a new reverse transcriptase, SuperScript® IV, and experiments we performed show that it is the most robust reverse transcriptase compared to other enzymes. SuperScript® IV characterization was performed in the context of “real world” situations where users do not have perfect RNA samples. In the presence of a variety of inhibitors, we demonstrate that SuperScript® IV possesses superior performance in a variety of inhibitors, such as alcohols, salts, detergents, phenol, heparin, hematin, bile salts, and formalin typically found in sample preparation reagents, cell lines, blood, feces, and FFPE samples. This enzyme can even detect RNA targets in unpurified RNA samples (directly lysed cells) and whole blood without sacrificing sensitivity and yield. The introduction of SuperScript® IV enables researchers to obtain more consistent results independent of sample quality and simplify and speed up workflows by eliminating RNA purification.
This document summarizes a study that evaluated gene expression profiling of 84 human drug metabolizing enzymes using a pathway-focused PCR array. Researchers treated human hepatocytes with 3 drugs and used the PCR array to measure mRNA expression. They found high intra- and inter-laboratory reproducibility of the PCR array results based on correlation of ΔCT and ΔΔCT values and overlap of differentially expressed genes between experiments. Comparison to TaqMan data also showed high concordance, validating the PCR array as a reliable tool for quantifying drug metabolizing gene expression.
2015 - Cdk5 promotes DNA replication stress checkpoint activation through RPA...Simon Gemble
Cdk5 promotes DNA replication stress checkpoint activation through RPA-32 phosphorylation, and impacts metastasis free survival in breast cancer patients. The study found that depletion of Cdk5 in cells results in increased sensitivity to agents that cause replication stress, slower DNA replication, and impaired activation of the intra-S phase DNA damage checkpoint. Cdk5 was shown to directly phosphorylate RPA32 on residues necessary for checkpoint activation. Analysis of breast cancer patient data revealed that lower levels of Cdk5 correlated with longer metastasis free survival after treatment. The results suggest that Cdk5 plays a role in DNA replication and repair, and that its depletion could enhance killing of tumor cells by therapies like radiation and PARP inhibitors.
Cloning of the c dna for thyroid stimulating hormone subunit and changes in a...rubycharlie
1) The researchers cloned the cDNA for the thyroid stimulating hormone beta subunit (TSHβ) of the Japanese eel (Anguilla japonica) and investigated changes in the pituitary-thyroid axis during silvering.
2) They found the TSHβ gene contains two introns and three exons, and the protein has a signal peptide and mature peptide. The TSHβ sequence is highly similar to other fish species.
3) In vitro, thyrotropin-releasing hormone increased while thyroxine decreased TSHβ mRNA expression in cultured pituitaries. TSHβ mRNA and serum thyroxine levels both increased during silvering in wild female eels, supporting the
The document summarizes work done on cloning, expressing, and purifying the sigma 54 transcription factor from Pseudomonas aeruginosa. Key steps included PCR amplification of the sigma 54 gene, cloning it into expression vectors, confirming clones, optimizing expression conditions, and purifying the protein using affinity and size exclusion chromatography. A truncated version of sigma 54 was also generated and purified. Binding assays were performed between sigma 54 and the transcriptional activator FleQ, but the interaction was not clearly demonstrated.
This document discusses cancer drug targets and profiling key genes related to cancer treatment. It begins with an overview of actively investigated cancer drug target genes across various categories like growth factors and receptors, protein kinases, apoptosis genes, and more. It then discusses profiling gene expressions using RT2 Profiler PCR Arrays which allow analyzing 84 pathway genes along with controls. The document also discusses detecting gene mutations using Cancer Mutation PCR Arrays designed around clinically relevant mutations. Finally, it discusses analyzing histone modifications of drug target genes using epigenetic approaches, as histone modifications influence gene transcription and cell response to drug regimens.
IRJET- Silencing of hnRNP A1 and hnRNP A2/B1 Downregulates the Expression of ...IRJET Journal
The document summarizes a study that examined the effect of silencing hnRNP A1 and hnRNP A2/B1 splice factors on the expression of CD44v6 and CD44v10 exons in glioma cells. The researchers found that knockdown of hnRNP A1 and hnRNP A2/B1 led to decreased expression of CD44v6 and CD44v10 exons based on qRT-PCR analysis. Specifically, cells with silenced splice factors had lower expression of the two exons compared to non-silenced control cells. Therefore, hnRNP A1 and hnRNP A2/B1 may positively regulate the expression of
A reading report for <A Secreted Slit2 Fragment Regulates Adipose Tissue Ther...星云 王
A reading report for <A Secreted Slit2 Fragment Regulates Adipose Tissue Thermogenesis and Metabolic Function
>, only for private study use, please do not use it for profit or public.
Fiorucci presents research on the role of bile acids and their activation of nuclear receptors such as FXR in regulating gastrointestinal mucosa integrity. Bile acids are endogenous ligands for FXR and other receptors that modulate inflammation. Activation of FXR was shown to reduce markers of colitis and inflammation in mouse models of inflammatory bowel disease. FXR deficient mice had increased inflammation and tissue damage compared to controls in response to colitis induction. Pharmacological FXR activation also reduced inflammation. This suggests FXR plays an important role in innate immunity and protection of the GI tract from inflammation.
Discriminating Facts from Artefacts in the Secreted Ly-6 Protein FamilyChris Southan
The document discusses several issues related to accurately characterizing the secreted Ly-6 protein family based on bioinformatic analysis. It describes the discovery of novel rat Ly-6 proteins from urine samples and EST data, but also finds chimeric mRNA sequences that combined portions of unrelated genes with Ly-6 sequences, complicating the analysis. Genome mapping showed the chimeras did not represent real gene fusions but likely arose from artifacts. While many rat and mouse homologs were identified, clear orthologs between species were difficult to determine due to high sequence divergence over time.
The document describes research into identifying potent inhibitors of the SHP2 protein tyrosine phosphatase. Several small molecule inhibitors were discovered, including NSC-87877, which was shown to selectively inhibit SHP2 activity in vitro and in cell-based assays. It was the first evidence that SHP2 phosphatase is involved in growth factor-stimulated ERK activation. Further screening of a chemical library identified additional SHP2 inhibitors, such as HLM002903 and HLM019544, which were shown to inhibit SHP2-dependent cell growth and signaling. The goal of finding SHP2 inhibitors is to develop potential anti-cancer agents, as SHP2 mutations have been implicated in various cancers and
1. The document discusses various pathways and receptors involved in bile acid metabolism and signaling, including the farnesoid X receptor (FXR).
2. It shows that glycyrrhizic acid, a component of licorice, is a potent FXR agonist in vitro.
3. Administration of glycyrrhizic acid was found to activate FXR signaling and protect against aspirin-induced gastric lesions in mice by increasing prostaglandin levels.
The document describes assays to demonstrate the mechanism of action of SXN101959, a targeted secretion inhibitor being developed for the treatment of acromegaly. It outlines cellular and in vivo assays to show that SXN101959 binds and activates growth hormone-releasing hormone receptors, is internalized into cells, cleaves SNARE proteins via its enzymatic domain, and inhibits pulsatile growth hormone secretion. A battery of assays using receptor expressing cell lines and pituicytes aims to validate the mechanism of action at each step in multiple preclinical species.
This document summarizes a study that analyzed the frequency of the CYP4F2 rs2108622 genetic variant among 90 healthy Jordanian volunteers. The study found:
- The frequency of the C allele was 0.55 and of the T allele was 0.45.
- The most common genotype was heterozygous CT at 0.55 frequency.
- The frequencies in Jordanians were similar to Caucasians but different from other groups like Africans.
- This variant may influence cardiovascular diseases and warfarin response in Jordanians.
This research project studied post-translational modifications (PTMs) of nicotinamide phosphoribosyltransferase (NAMPT) through site-directed mutagenesis. NAMPT is the rate-limiting enzyme in the NAD+ salvage pathway. The document details the cloning of NAMPT cDNA into expression vectors, generation of point mutations at various PTM sites, expression and purification of mutant proteins, and initial analysis. Future work will involve further mutagenesis and characterization of the mutated NAMPT proteins to better understand how PTMs regulate NAMPT activity and NAD+ regeneration.
Senior Thesis-Analyzing the interactions between MYOGEF and a component of er...Dougan McGrath
This document summarizes a study analyzing the interaction between MYOGEF, a guanine nucleotide exchange factor that activates RhoA, and SPTA1, a major component of the erythrocyte cytoskeleton. Previous research identified SPTA1 as an interacting partner of MYOGEF. The current study aims to characterize this interaction through constructing cDNA fragments of different regions of MYOGEF and SPTA1 and examining their interaction using yeast two-hybrid and in vitro pull-down assays. The results showed that the C-terminal region of MYOGEF interacted with the EF-hand motifs located in the C-terminal region of SPTA1. This interaction may lead to MYOGEF-mediated
The DIONESUS algorithm provides a scalable and accurate method to reconstruct dynamic phosphoproteomic networks and reveal new drug targets. The document describes an experiment where the DIONESUS algorithm was applied to phosphorylation kinetics data from panels of growth factors, small molecule inhibitors, and antioxidants tested on A431 cells. Inhibition of SRC family kinases or PLCγ pathways attenuated EGF-stimulated cell death, while inhibition of PI3K, autocrine signaling pathways, or antioxidants decreased cell viability. The phosphorylation profiles informed dynamic network modeling to infer signaling pathways and potential drug targets.
2014 lecture next generation metabolic screening - Marrakech Ron Wevers
Next Generation Metabolic Screening is a novel technique that can be applied to body fluids as urine, plasma or cerebrospinal fluid for the diagnosis of inborn errors of metabolism. The technique gives a holistic view on metabolism (metabolomics) and uses LC_Qtof mass spectrometry. The technique was developed in Nijmegen, The Netherlands in the group of Prof Ron Wevers (ron.wevers@radboudumc.nl)
The document describes research sequencing the human lymph peptidome using various mass spectrometry techniques. Over 900 peptides were identified from over 480 proteins. The peptides came from intracellular, extracellular, and membrane proteins. Some peptides bound strongly to MHC II molecules, indicating they could be immunologically relevant. Analysis of the molecular functions and pathways identified acute phase response and coagulation proteins. Protease processing pathways generating the peptidome involved matrix metalloproteases, cathepsins, and enzymes from innate immunity and coagulation. The study provides new insights into self-antigens and peptides presented by immune cells.
SuperScript IV Reverse Transcriptase for RNA Analysis | ESHG 2015 Poster PS14...Thermo Fisher Scientific
Survey and interview studies conducted over a three year period revealed that researchers are not satisfied with their current reverse transcriptase and are performing reactions with increasingly difficult samples, such as poorly purified RNA and unpurified RNA (direct RT) that both contain inhibitors. To meet this performance gap, the Thermo Fisher Life Sciences Solutions group produced a new reverse transcriptase, SuperScript® IV, and experiments we performed show that it is the most robust reverse transcriptase compared to other enzymes. SuperScript® IV characterization was performed in the context of “real world” situations where users do not have perfect RNA samples. In the presence of a variety of inhibitors, we demonstrate that SuperScript® IV possesses superior performance in a variety of inhibitors, such as alcohols, salts, detergents, phenol, heparin, hematin, bile salts, and formalin typically found in sample preparation reagents, cell lines, blood, feces, and FFPE samples. This enzyme can even detect RNA targets in unpurified RNA samples (directly lysed cells) and whole blood without sacrificing sensitivity and yield. The introduction of SuperScript® IV enables researchers to obtain more consistent results independent of sample quality and simplify and speed up workflows by eliminating RNA purification.
This document summarizes a study that evaluated gene expression profiling of 84 human drug metabolizing enzymes using a pathway-focused PCR array. Researchers treated human hepatocytes with 3 drugs and used the PCR array to measure mRNA expression. They found high intra- and inter-laboratory reproducibility of the PCR array results based on correlation of ΔCT and ΔΔCT values and overlap of differentially expressed genes between experiments. Comparison to TaqMan data also showed high concordance, validating the PCR array as a reliable tool for quantifying drug metabolizing gene expression.
2015 - Cdk5 promotes DNA replication stress checkpoint activation through RPA...Simon Gemble
Cdk5 promotes DNA replication stress checkpoint activation through RPA-32 phosphorylation, and impacts metastasis free survival in breast cancer patients. The study found that depletion of Cdk5 in cells results in increased sensitivity to agents that cause replication stress, slower DNA replication, and impaired activation of the intra-S phase DNA damage checkpoint. Cdk5 was shown to directly phosphorylate RPA32 on residues necessary for checkpoint activation. Analysis of breast cancer patient data revealed that lower levels of Cdk5 correlated with longer metastasis free survival after treatment. The results suggest that Cdk5 plays a role in DNA replication and repair, and that its depletion could enhance killing of tumor cells by therapies like radiation and PARP inhibitors.
Cloning of the c dna for thyroid stimulating hormone subunit and changes in a...rubycharlie
1) The researchers cloned the cDNA for the thyroid stimulating hormone beta subunit (TSHβ) of the Japanese eel (Anguilla japonica) and investigated changes in the pituitary-thyroid axis during silvering.
2) They found the TSHβ gene contains two introns and three exons, and the protein has a signal peptide and mature peptide. The TSHβ sequence is highly similar to other fish species.
3) In vitro, thyrotropin-releasing hormone increased while thyroxine decreased TSHβ mRNA expression in cultured pituitaries. TSHβ mRNA and serum thyroxine levels both increased during silvering in wild female eels, supporting the
The document summarizes work done on cloning, expressing, and purifying the sigma 54 transcription factor from Pseudomonas aeruginosa. Key steps included PCR amplification of the sigma 54 gene, cloning it into expression vectors, confirming clones, optimizing expression conditions, and purifying the protein using affinity and size exclusion chromatography. A truncated version of sigma 54 was also generated and purified. Binding assays were performed between sigma 54 and the transcriptional activator FleQ, but the interaction was not clearly demonstrated.
This document discusses cancer drug targets and profiling key genes related to cancer treatment. It begins with an overview of actively investigated cancer drug target genes across various categories like growth factors and receptors, protein kinases, apoptosis genes, and more. It then discusses profiling gene expressions using RT2 Profiler PCR Arrays which allow analyzing 84 pathway genes along with controls. The document also discusses detecting gene mutations using Cancer Mutation PCR Arrays designed around clinically relevant mutations. Finally, it discusses analyzing histone modifications of drug target genes using epigenetic approaches, as histone modifications influence gene transcription and cell response to drug regimens.
IRJET- Silencing of hnRNP A1 and hnRNP A2/B1 Downregulates the Expression of ...IRJET Journal
The document summarizes a study that examined the effect of silencing hnRNP A1 and hnRNP A2/B1 splice factors on the expression of CD44v6 and CD44v10 exons in glioma cells. The researchers found that knockdown of hnRNP A1 and hnRNP A2/B1 led to decreased expression of CD44v6 and CD44v10 exons based on qRT-PCR analysis. Specifically, cells with silenced splice factors had lower expression of the two exons compared to non-silenced control cells. Therefore, hnRNP A1 and hnRNP A2/B1 may positively regulate the expression of
Please note: This presentation accompanies a recorded webinar at:
https://www1.gotomeeting.com/register/347794241
Biomarkers for studying gene regulation and cell function can be efficiently analyzed by multiplexed methods. Dr. Jim Lazar from OriGene Technologies will provide an overview of four different but related detection technologies that can be used to analyze genetic variants, microRNA expression, transcription factor binding, and protein expression on the Luminex xMAP platform. OriGene’s broad panel of assays and tools for discovery, analysis and validation of multiple classes of important biomarkers will allow researcher to develop more accurate descriptions of biologically complex systems.
This document describes the development of a prototype synthetic microRNA mixture intended for use as a spike-in control for microRNA profiling platforms. 32 microRNAs were selected based on certain criteria and synthesized. The microRNAs were pooled and combined in varying concentrations according to a Latin Square design to generate 8 control mixtures spanning a 4-log dynamic range. Initial testing on PCR arrays showed the control mixtures generated heterologous calibration curves comparable to homogeneous controls for assessing platform performance. The synthetic microRNA control has the potential to help evaluate various performance characteristics of microRNA profiling platforms.
Oncodesign aacr 2018 development of a high throughput in vitro screening pl...Florence Fombertasse
Immunological cell death (ICD) is a form of cancer cell death induced by radiotherapy, photodynamic therapy and a few chemotherapeutic agents such as Doxorubicin, Mitoxantrone, and Oxaliplatin. Unlike apoptosis or necrosis, ICD can induce an effective immune response directed against the tumor whereby both dendritic cells and T lymphocytes are mediators of this response. Dying cancer cells recruit and activate immune cells by releasing damage-associated molecular patterns (DAMPS) that help and promote the immune response to antigenic tumor neo-epitopes. Three key DAMPS are associated with the ICD process: calreticulin exposition on the cell surface, ATP secretion and high-mobility group box 1 (HMGB1) release. In order to identify new therapeutic agents that promote ICD in malignant cells, we developed a screening strategy facilitated by an automated in vitro platform with four assays on three different tumor cell lines (human osteosarcoma U-2 OS, human breast MDA-MB-231 and murine liver Hepa 1-6). ICD inducers Doxorubicin and Mitoxantrone used as positive controls increased ATP secretion by 2 to 10-fold at a non-cytotoxic dose after 72 hours incubation on the three cell lines. Both compounds also increased calreticulin exposition by 2 to 4-fold (determined by immunofluorescence using the Operetta High-Content Imaging System) and HMGB1 release by two-fold on the three cell lines. Here we will present recent data from the screening of Oncodesign’s Nanocyclix® library using this platform to identify novel ICD inducers.
Technical Guide to Qiagen PCR Arrays - Download the GuideQIAGEN
Total RNA discovery with RT2 and miScript PCR Arrays : Explore the RNA universe - Whatever your destination within the RNA universe, QIAGEN will help you get there. The miRNeasy kits deliver pure, high-quality total RNA from a broad range of samples. The RT2 and miScript PCR arrays are a complete solution both for focused analysis of gene and microRNA expression and for validation of microarray and RNA sequencing experiments. Together with the powerful analytics tools of GeneGlobe® and QIAGEN Ingenuity® Pathway Analysis, these products give you a smooth path from your sample to high-quality results.
RT2 Profiler PCR Arrays allow researchers to analyze gene expression in biological pathways or disease states using real-time PCR. The document discusses:
1. PCR Arrays focus on profiling genes relevant to specific pathways or disease states. They provide a simple, reproducible, and sensitive way to simultaneously profile expression of many genes related to a pathway.
2. Examples are provided demonstrating how PCR Arrays have been used in cancer research to discover breast cancer biomarkers, in immunology research to monitor cytokine induction, and in toxicity research to determine drug toxicity profiles.
3. Key advantages of PCR Arrays are highlighted, including their simplicity, performance, relevance to specific pathways, and ability to analyze gene expression from small amounts
DNA Microarray and Analysis of Metabolic Controlshilpa sharma
This document describes a study that used DNA microarrays to analyze changes in gene expression related to tryptophan metabolism in E. coli under different physiological conditions and genetic mutations. The study identified genes whose expression levels changed with tryptophan availability, tryptophan starvation, and inactivation of the tryptophan repressor. Only a small core set of operons including trp, mtr and aroH showed highly responsive changes in expression levels. mRNA levels for aromatic amino acid biosynthesis genes decreased with excess tryptophan, while only the tnaA-tnaB operon increased. The results provide quantitative validation of genes known to be involved in tryptophan metabolism.
Next generation sequencing of the whole transcriptome enables high resolution measurement of gene expression activity in different tissue and cell types. This methodology provides an in depth study of known transcripts and depending on the data analysis, allows identification of additional transcript types such as transcript variants, fusion transcripts, and small and long ncRNAs.
In this study we performed RNA-Seq using the Ion Torrent™ sequencing platform to compare the expression profile of testicular germ cell cancers (seminoma type, n=3) and normal testis (n=3). Using Partek Flow® 3.0 and TopHat/BowTie or Star aligners, we aligned the reads to the human genome and mapped sequences to the RefSeq database. Differentially expressed genes were identified and screened with additional germ cell tumors.
PCA analysis showed clear separation of the two sample types indicating biological differences. List of differentially expressed genes generated from TopHat/Bowtie and Star were similar. We identified a large number of genes that were up and down regulated with high degree of significance (p<0.01,>2X FC (fold change)). These included genes related to testicular tissue type, stem cell pluripotency (NANOG; POU5F1) and proliferation (KRAS, CCND2).
In addition, a number of differentially expressed noncoding RNAs were identified (SNORD12B, XIST). The method was validated on a small set of genes (n=20) using qPCR (TaqMan® Assays) and were found to be correlated. We used the OpenArray® platform to quickly and quantitatively screen 102 differentially expressed genes and 10 endogenous control genes across a number of different testicular germ cell cancer types.
We used a complete work flow solution from sample prep to NGS to qPCR to compare the expression profile of normal testis and seminoma type germ cell tumors. From the NGS experiments we identified a large number of differentially expressed genes for qPCR screening with samples from different types of germ cell tumors. Results from these screening studies will be presented.
Two-Tailed PCR - New Ultrasensitive and Ultraspecific Technique for the Quant...Kate Barlow
This document discusses methods for quantifying and analyzing microRNAs (miRNAs) using quantitative PCR (qPCR). It presents a new two-tailed RT-qPCR method that provides high sensitivity and specificity for detecting miRNAs, including discrimination of miRNA isoforms. The method allows unlimited multiplexing in the reverse transcription step followed by singleplex qPCR. The document benchmarks the two-tailed RT-qPCR method on biological samples, showing it can sensitively detect less than 10 molecules and maintain specificity across the entire miRNA sequence. It also demonstrates two-tube multiplexing of the method to profile expression levels of several miRNAs in different tissues.
This document describes a real-time PCR array for simultaneously evaluating the expression of multiple cytokine mRNAs. The RT2Profiler PCR Array allows detection of 84 cytokine-related genes with high reproducibility, specificity, efficiency and sensitivity. The array was used to identify cytokines upregulated or downregulated in peripheral blood mononuclear cells stimulated with PMA and ionomycin compared to unstimulated cells. Twenty-nine genes showed at least a 5-fold change in expression, and protein level changes measured by ELISA were consistent with mRNA changes detected by the array. The PCR array provides a reliable tool for profiling cytokine gene expression.
This document describes a real-time PCR array for simultaneously evaluating the expression of multiple cytokine mRNAs. The RT2Profiler PCR Array demonstrated high reproducibility, specificity, efficiency, sensitivity, and linear dynamic range. Using this array, 29 genes were found to have at least a 5-fold change in expression between resting and stimulated peripheral blood mononuclear cells after 6 hours of stimulation. The array provides a reliable tool for profiling cytokine pathway gene expression.
1. The ChampionChIP system allows for epigenetic analysis of histone modifications and transcription factor binding in a single day. It uses validated antibodies, primers, and qPCR arrays to analyze multiple genomic regions simultaneously.
2. The system was used to analyze dynamic bivalent histone modification patterns of pluripotency genes during mouse embryonic carcinoma cell differentiation induced by retinoic acid. Distinct patterns were observed for genes and heterochromatic regions.
3. The system correctly identified histone modification distribution and was used to map modifications around the CDKN1A gene. It also analyzed p53 binding and correlated gene expression changes in response to drug treatment in cancer cell lines.
This document discusses ChIP-Atlas, a database of chromatin immunoprecipitation sequencing (ChIP-seq) data. It contains over 1,000 TB of ChIP-seq data from thousands of experiments profiling transcription factor and histone modifications across various cell types. The database can be used to identify transcription factors enriched at tissue-specific genes and provides tools to analyze ChIP-seq data, including a peak browser and enrichment analysis. It aims to facilitate understanding of gene regulation networks in different cell types.
The document provides an overview of real-time PCR (polymerase chain reaction). It discusses extracting RNA from tissue, converting the RNA to cDNA using reverse transcriptase, performing real-time PCR, and analyzing the results. Several key steps are described, including the importance of RNA quality, using appropriate reverse transcriptase primers and PCR primers, including necessary controls, and selecting appropriate reference standards for normalization.
The document describes a study that analyzed gene expression data from ovarian carcinoma cell lines treated with and without the chemotherapy drug cisplatin. The study aimed to explore the connection between cellular responses to cisplatin and epithelial-mesenchymal transition (EMT). Gene expression microarrays were used to analyze 171 samples and identify differentially expressed genes between epithelial-like and mesenchymal-like cell lines. Statistical tests identified over 6500 differentially expressed genes. Classification analysis correctly predicted the epithelial or mesenchymal status of 70 test samples based on their gene expression profiles. Top genes found to be upregulated or downregulated in epithelial versus mesenchymal cell lines are involved in processes like cell adhesion, migration and proliferation
The document summarizes research evaluating the performance of TaqMan Low Density Arrays for gene expression analysis. It finds that assays on arrays can discriminate 2-fold changes as well as plate assays, and assay results are highly reproducible both within and across arrays. The study also uses a TaqMan Low Density Human Endogenous Control Array to examine housekeeping gene expression across 32 tissues, identifying genes with consistent expression levels suitable for normalization.
A novel platform for in situ, multiomic, hyper-plexed analyses of systems bio...Rafael Casiano
The document describes a novel platform called MultiOmyx that enables simultaneous imaging of protein and nucleic acid biomarkers at a subcellular level in tissue samples. It allows for quantification of biomarkers in individual cells while preserving spatial architecture. Analysis of a colon cancer cohort revealed extensive immune cell heterogeneity between patients and unexpected patterns of signal transduction pathway activation at single cell levels. This highlights the unique capability of MultiOmyx to provide novel insights into biological mechanisms through multiomic, hyper-plexed tissue analysis.
Reporter assay and q pcr application 2012Elsa von Licy
This document summarizes a presentation on high-performance cell-based assay and qPCR technologies for pathway-focused research. The presentation overview discusses QIAGEN's SABiosciences portfolio, PCR arrays, Cignal and Cignal Lenti pathway reporters, and provides a summary. PCR arrays allow analysis of mRNA expression of up to 84 genes related to biological pathways in a single experiment. Cignal reporter assays use dual-luciferase reporters to study 45 signal transduction pathways. Cignal Lenti reporters use lentiviral delivery of luciferase or GFP reporters to study pathways in difficult to transfect cells like stem cells or primary cells.
For the full video of this presentation, please visit: https://www.edge-ai-vision.com/2024/06/building-and-scaling-ai-applications-with-the-nx-ai-manager-a-presentation-from-network-optix/
Robin van Emden, Senior Director of Data Science at Network Optix, presents the “Building and Scaling AI Applications with the Nx AI Manager,” tutorial at the May 2024 Embedded Vision Summit.
In this presentation, van Emden covers the basics of scaling edge AI solutions using the Nx tool kit. He emphasizes the process of developing AI models and deploying them globally. He also showcases the conversion of AI models and the creation of effective edge AI pipelines, with a focus on pre-processing, model conversion, selecting the appropriate inference engine for the target hardware and post-processing.
van Emden shows how Nx can simplify the developer’s life and facilitate a rapid transition from concept to production-ready applications.He provides valuable insights into developing scalable and efficient edge AI solutions, with a strong focus on practical implementation.
Webinar: Designing a schema for a Data WarehouseFederico Razzoli
Are you new to data warehouses (DWH)? Do you need to check whether your data warehouse follows the best practices for a good design? In both cases, this webinar is for you.
A data warehouse is a central relational database that contains all measurements about a business or an organisation. This data comes from a variety of heterogeneous data sources, which includes databases of any type that back the applications used by the company, data files exported by some applications, or APIs provided by internal or external services.
But designing a data warehouse correctly is a hard task, which requires gathering information about the business processes that need to be analysed in the first place. These processes must be translated into so-called star schemas, which means, denormalised databases where each table represents a dimension or facts.
We will discuss these topics:
- How to gather information about a business;
- Understanding dictionaries and how to identify business entities;
- Dimensions and facts;
- Setting a table granularity;
- Types of facts;
- Types of dimensions;
- Snowflakes and how to avoid them;
- Expanding existing dimensions and facts.
OpenID AuthZEN Interop Read Out - AuthorizationDavid Brossard
During Identiverse 2024 and EIC 2024, members of the OpenID AuthZEN WG got together and demoed their authorization endpoints conforming to the AuthZEN API
Unlock the Future of Search with MongoDB Atlas_ Vector Search Unleashed.pdfMalak Abu Hammad
Discover how MongoDB Atlas and vector search technology can revolutionize your application's search capabilities. This comprehensive presentation covers:
* What is Vector Search?
* Importance and benefits of vector search
* Practical use cases across various industries
* Step-by-step implementation guide
* Live demos with code snippets
* Enhancing LLM capabilities with vector search
* Best practices and optimization strategies
Perfect for developers, AI enthusiasts, and tech leaders. Learn how to leverage MongoDB Atlas to deliver highly relevant, context-aware search results, transforming your data retrieval process. Stay ahead in tech innovation and maximize the potential of your applications.
#MongoDB #VectorSearch #AI #SemanticSearch #TechInnovation #DataScience #LLM #MachineLearning #SearchTechnology
In the rapidly evolving landscape of technologies, XML continues to play a vital role in structuring, storing, and transporting data across diverse systems. The recent advancements in artificial intelligence (AI) present new methodologies for enhancing XML development workflows, introducing efficiency, automation, and intelligent capabilities. This presentation will outline the scope and perspective of utilizing AI in XML development. The potential benefits and the possible pitfalls will be highlighted, providing a balanced view of the subject.
We will explore the capabilities of AI in understanding XML markup languages and autonomously creating structured XML content. Additionally, we will examine the capacity of AI to enrich plain text with appropriate XML markup. Practical examples and methodological guidelines will be provided to elucidate how AI can be effectively prompted to interpret and generate accurate XML markup.
Further emphasis will be placed on the role of AI in developing XSLT, or schemas such as XSD and Schematron. We will address the techniques and strategies adopted to create prompts for generating code, explaining code, or refactoring the code, and the results achieved.
The discussion will extend to how AI can be used to transform XML content. In particular, the focus will be on the use of AI XPath extension functions in XSLT, Schematron, Schematron Quick Fixes, or for XML content refactoring.
The presentation aims to deliver a comprehensive overview of AI usage in XML development, providing attendees with the necessary knowledge to make informed decisions. Whether you’re at the early stages of adopting AI or considering integrating it in advanced XML development, this presentation will cover all levels of expertise.
By highlighting the potential advantages and challenges of integrating AI with XML development tools and languages, the presentation seeks to inspire thoughtful conversation around the future of XML development. We’ll not only delve into the technical aspects of AI-powered XML development but also discuss practical implications and possible future directions.
How to Get CNIC Information System with Paksim Ga.pptxdanishmna97
Pakdata Cf is a groundbreaking system designed to streamline and facilitate access to CNIC information. This innovative platform leverages advanced technology to provide users with efficient and secure access to their CNIC details.
AI 101: An Introduction to the Basics and Impact of Artificial IntelligenceIndexBug
Imagine a world where machines not only perform tasks but also learn, adapt, and make decisions. This is the promise of Artificial Intelligence (AI), a technology that's not just enhancing our lives but revolutionizing entire industries.
Cosa hanno in comune un mattoncino Lego e la backdoor XZ?Speck&Tech
ABSTRACT: A prima vista, un mattoncino Lego e la backdoor XZ potrebbero avere in comune il fatto di essere entrambi blocchi di costruzione, o dipendenze di progetti creativi e software. La realtà è che un mattoncino Lego e il caso della backdoor XZ hanno molto di più di tutto ciò in comune.
Partecipate alla presentazione per immergervi in una storia di interoperabilità, standard e formati aperti, per poi discutere del ruolo importante che i contributori hanno in una comunità open source sostenibile.
BIO: Sostenitrice del software libero e dei formati standard e aperti. È stata un membro attivo dei progetti Fedora e openSUSE e ha co-fondato l'Associazione LibreItalia dove è stata coinvolta in diversi eventi, migrazioni e formazione relativi a LibreOffice. In precedenza ha lavorato a migrazioni e corsi di formazione su LibreOffice per diverse amministrazioni pubbliche e privati. Da gennaio 2020 lavora in SUSE come Software Release Engineer per Uyuni e SUSE Manager e quando non segue la sua passione per i computer e per Geeko coltiva la sua curiosità per l'astronomia (da cui deriva il suo nickname deneb_alpha).
Driving Business Innovation: Latest Generative AI Advancements & Success StorySafe Software
Are you ready to revolutionize how you handle data? Join us for a webinar where we’ll bring you up to speed with the latest advancements in Generative AI technology and discover how leveraging FME with tools from giants like Google Gemini, Amazon, and Microsoft OpenAI can supercharge your workflow efficiency.
During the hour, we’ll take you through:
Guest Speaker Segment with Hannah Barrington: Dive into the world of dynamic real estate marketing with Hannah, the Marketing Manager at Workspace Group. Hear firsthand how their team generates engaging descriptions for thousands of office units by integrating diverse data sources—from PDF floorplans to web pages—using FME transformers, like OpenAIVisionConnector and AnthropicVisionConnector. This use case will show you how GenAI can streamline content creation for marketing across the board.
Ollama Use Case: Learn how Scenario Specialist Dmitri Bagh has utilized Ollama within FME to input data, create custom models, and enhance security protocols. This segment will include demos to illustrate the full capabilities of FME in AI-driven processes.
Custom AI Models: Discover how to leverage FME to build personalized AI models using your data. Whether it’s populating a model with local data for added security or integrating public AI tools, find out how FME facilitates a versatile and secure approach to AI.
We’ll wrap up with a live Q&A session where you can engage with our experts on your specific use cases, and learn more about optimizing your data workflows with AI.
This webinar is ideal for professionals seeking to harness the power of AI within their data management systems while ensuring high levels of customization and security. Whether you're a novice or an expert, gain actionable insights and strategies to elevate your data processes. Join us to see how FME and AI can revolutionize how you work with data!
Programming Foundation Models with DSPy - Meetup SlidesZilliz
Prompting language models is hard, while programming language models is easy. In this talk, I will discuss the state-of-the-art framework DSPy for programming foundation models with its powerful optimizers and runtime constraint system.
Monitoring and Managing Anomaly Detection on OpenShift.pdfTosin Akinosho
Monitoring and Managing Anomaly Detection on OpenShift
Overview
Dive into the world of anomaly detection on edge devices with our comprehensive hands-on tutorial. This SlideShare presentation will guide you through the entire process, from data collection and model training to edge deployment and real-time monitoring. Perfect for those looking to implement robust anomaly detection systems on resource-constrained IoT/edge devices.
Key Topics Covered
1. Introduction to Anomaly Detection
- Understand the fundamentals of anomaly detection and its importance in identifying unusual behavior or failures in systems.
2. Understanding Edge (IoT)
- Learn about edge computing and IoT, and how they enable real-time data processing and decision-making at the source.
3. What is ArgoCD?
- Discover ArgoCD, a declarative, GitOps continuous delivery tool for Kubernetes, and its role in deploying applications on edge devices.
4. Deployment Using ArgoCD for Edge Devices
- Step-by-step guide on deploying anomaly detection models on edge devices using ArgoCD.
5. Introduction to Apache Kafka and S3
- Explore Apache Kafka for real-time data streaming and Amazon S3 for scalable storage solutions.
6. Viewing Kafka Messages in the Data Lake
- Learn how to view and analyze Kafka messages stored in a data lake for better insights.
7. What is Prometheus?
- Get to know Prometheus, an open-source monitoring and alerting toolkit, and its application in monitoring edge devices.
8. Monitoring Application Metrics with Prometheus
- Detailed instructions on setting up Prometheus to monitor the performance and health of your anomaly detection system.
9. What is Camel K?
- Introduction to Camel K, a lightweight integration framework built on Apache Camel, designed for Kubernetes.
10. Configuring Camel K Integrations for Data Pipelines
- Learn how to configure Camel K for seamless data pipeline integrations in your anomaly detection workflow.
11. What is a Jupyter Notebook?
- Overview of Jupyter Notebooks, an open-source web application for creating and sharing documents with live code, equations, visualizations, and narrative text.
12. Jupyter Notebooks with Code Examples
- Hands-on examples and code snippets in Jupyter Notebooks to help you implement and test anomaly detection models.
5th LF Energy Power Grid Model Meet-up SlidesDanBrown980551
5th Power Grid Model Meet-up
It is with great pleasure that we extend to you an invitation to the 5th Power Grid Model Meet-up, scheduled for 6th June 2024. This event will adopt a hybrid format, allowing participants to join us either through an online Mircosoft Teams session or in person at TU/e located at Den Dolech 2, Eindhoven, Netherlands. The meet-up will be hosted by Eindhoven University of Technology (TU/e), a research university specializing in engineering science & technology.
Power Grid Model
The global energy transition is placing new and unprecedented demands on Distribution System Operators (DSOs). Alongside upgrades to grid capacity, processes such as digitization, capacity optimization, and congestion management are becoming vital for delivering reliable services.
Power Grid Model is an open source project from Linux Foundation Energy and provides a calculation engine that is increasingly essential for DSOs. It offers a standards-based foundation enabling real-time power systems analysis, simulations of electrical power grids, and sophisticated what-if analysis. In addition, it enables in-depth studies and analysis of the electrical power grid’s behavior and performance. This comprehensive model incorporates essential factors such as power generation capacity, electrical losses, voltage levels, power flows, and system stability.
Power Grid Model is currently being applied in a wide variety of use cases, including grid planning, expansion, reliability, and congestion studies. It can also help in analyzing the impact of renewable energy integration, assessing the effects of disturbances or faults, and developing strategies for grid control and optimization.
What to expect
For the upcoming meetup we are organizing, we have an exciting lineup of activities planned:
-Insightful presentations covering two practical applications of the Power Grid Model.
-An update on the latest advancements in Power Grid -Model technology during the first and second quarters of 2024.
-An interactive brainstorming session to discuss and propose new feature requests.
-An opportunity to connect with fellow Power Grid Model enthusiasts and users.
Your One-Stop Shop for Python Success: Top 10 US Python Development Providersakankshawande
Simplify your search for a reliable Python development partner! This list presents the top 10 trusted US providers offering comprehensive Python development services, ensuring your project's success from conception to completion.
Threats to mobile devices are more prevalent and increasing in scope and complexity. Users of mobile devices desire to take full advantage of the features
available on those devices, but many of the features provide convenience and capability but sacrifice security. This best practices guide outlines steps the users can take to better protect personal devices and information.
Ivanti’s Patch Tuesday breakdown goes beyond patching your applications and brings you the intelligence and guidance needed to prioritize where to focus your attention first. Catch early analysis on our Ivanti blog, then join industry expert Chris Goettl for the Patch Tuesday Webinar Event. There we’ll do a deep dive into each of the bulletins and give guidance on the risks associated with the newly-identified vulnerabilities.
Introduction of Cybersecurity with OSS at Code Europe 2024Hiroshi SHIBATA
I develop the Ruby programming language, RubyGems, and Bundler, which are package managers for Ruby. Today, I will introduce how to enhance the security of your application using open-source software (OSS) examples from Ruby and RubyGems.
The first topic is CVE (Common Vulnerabilities and Exposures). I have published CVEs many times. But what exactly is a CVE? I'll provide a basic understanding of CVEs and explain how to detect and handle vulnerabilities in OSS.
Next, let's discuss package managers. Package managers play a critical role in the OSS ecosystem. I'll explain how to manage library dependencies in your application.
I'll share insights into how the Ruby and RubyGems core team works to keep our ecosystem safe. By the end of this talk, you'll have a better understanding of how to safeguard your code.
Introduction of Cybersecurity with OSS at Code Europe 2024
DTEx 02042009
1. DTExtm Gene Expression Analysis
Microarray based method - 768 element array
145 genes - 4 elements per gene
12 grids - 64 elements [16 x 4] per grid
All DTExtm genes are involved in drug metabolism, conjugation or transport
* interrogate for both reported and unreported drug effects on gene expression
* investigate coordinate regulation of gene expression, protein expression and functional activity
* all genes are RefSeq entries verified by NCBI with published literature history
All DTExtm genes are members of coordinate regulatory pathways
* internal control for induction or suppression of gene expression
* control for drug selectivity or specificity in the modulation of gene expression
DTExtm microarray is an ADME gene expression survey and screening method
* analysis of ADME gene expression signature(s) for cell or cell line characterisation and comparison
* analysis of ADME gene expression signature(s) and associated effects in drug treated cells or cell lines
- isogenic cancer cell lines
- hepatocytes
- tissue surrogates [HepaRG, Fa2N-4, etc.]
- tissues [liver, kidney, brain, eye, etc.]
DTExtm microarray analysis is reliable and reproducible
* either biological replicates or experimental replicates
2. ADME and DTExtm Microarray Analysis
The regulation of gene expression of various phase I enzymes, phase
II enzymes and phase III transporters has significant potential impact
on the metabolism, elimination, pharmacokinetics / dynamics,
toxicokinetics / dynamics and drug-drug interactions of many
therapeutic agents, as well as their ability to protect the human body
against exposure to environmental xenobiotics.
(Kong 2002, Guengerich 2003, LeCluyse 2003, Kong 2005)
4. DTExtm Microarray Analysis
What is DTExtm?
A method that allows the simultaneous analysis of changes in the levels
of gene expression of 145 ADME associated genes.
How is DTExtm done?
Total RNA converted to cDNA > cDNA coverted to aRNA > aRNA
converted to labelled cDNA > hybridise to DTExtm microarray > scan >
quantitation > first pass data analysis > second pass data analysis >
differential gene expression analysis [induction, suppression].
Why use DTExtm?
Survey basal level gene expression in various primary cells, cell lines or
tissues as a prelude to induction, inhibition or toxicity testing.
Survey coordinated changes in the levels of gene expression in various
primary cells, cell lines or tissues as a consequence of drug treatment.
5. DTExtm Microarray Gene Set
Gene Group Phase Group Members Number
Cytochrome P450s I 1A, 1B, 2A, 2B, 2C, 2D, 2E, 3A, 4A, 18
[CYPs] 4B, 7A, 8B, 19A, 27A, 27B
Nuclear Xenobiotic I AHR, AR, CAR, FXR, HNF, LXR, 19
Receptors [NXRs] NFE, NRF, PPAR, PXR, RXR, VDR
Sulfotransferases II 1A, 1B, 1C, 1E, 2A, 2B 6
[SULTs]
UDP glucuronosyl II 1A, 2A, 2B, 8 6
transferases [UGTs]
SLC (uptake) III CNT, ENT, LST, NTCP, OAT, OATP, 36
transporters [SLCs] OCT, OCTN, OST, PEPT, PGT,
URAT
ABC (efflux) III A, B, C, D, E, F, G 49
transporters [ABCs]
Controls 18S, 28S, ACT, B2M, GDH, S28, 11
SH1, SH2, RPLP0, TUB, VIL1
6. DTExtm Microarray Analysis
What is DTExtm?
A method that allows the simultaneous analysis of changes in the levels
of gene expression of 145 ADME associated genes.
How is DTExtm done?
Total RNA converted to cDNA > cDNA converted to aRNA > aRNA
converted to labelled cDNA > hybridise to DTExtm microarray > scan >
quantitation > first pass data analysis > second pass data analysis >
differential gene expression analysis [induction, suppression].
Why use DTExtm?
Survey basal level gene expression in various primary cells, cell lines or
tissues as a prelude to induction, inhibition or toxicity testing.
Survey coordinated changes in the levels of gene expression in various
primary cells, cell lines or tissues as a consequence of drug treatment.
7. DTExtm Microarray Analysis
What is DTExtm?
A method that allows the simultaneous analysis of changes in the levels of gene
expression of 145 ADME associated genes.
How is DTExtm done?
Total RNA converted to cDNA > cDNA coverted to aRNA > aRNA
converted to labelled cDNA > hybridise to DTExtm microarray > scan >
quantitation > first pass data analysis > second pass data analysis >
differential gene expression analysis [induction, suppression].
Why use DTExtm?
Survey basal level gene expression of all 145 ADME associated genes in various
primary cells, cell lines or tissues as a prelude to induction, inhibition or toxicity
testing.
Survey coordinated changes in the levels of gene expression in various primary
cells, cell lines or tissues as a consequence of drug treatment.
8. Basal level DTExtm gene expression in human hepatocytes
Matrix plot of relative level of gene expression data
Cluster plot of relative level of gene expression data
9. DTExtm Microarray Analysis
What is DTExtm?
A method that allows the simultaneous analysis of changes in the levels of gene
expression of 145 ADME associated genes.
How is DTExtm done?
Total RNA converted to cDNA > cDNA coverted to aRNA > aRNA
converted to labelled cDNA > hybridise to DTExtm microarray > scan >
quantitation > first pass data analysis > second pass data analysis >
differential gene expression analysis [induction, suppression].
Why use DTExtm?
Survey basal level gene expression of all 145 ADME associated genes in various
primary cells, cell lines or tissues as a prelude to induction, inhibition or toxicity
testing.
Survey coordinated changes in the levels of gene expression for all 145 ADME
associated genes in various primary cells, cell lines or tissues as a consequence
of drug treatment.
10. DTExtm gene expression in six rifampicin treated human hepatocyte lots
Matrix plot of relative level of gene expression data [range = 0-60x actin]
Cluster plot of relative level of gene expression data [range = 0-60x actin]
11. Induction of DTExtm gene expression in six rifampicin treated human hepatocyte lots
Matrix plot of relative level of gene expression induction [range = 0-4x vehicle treated]
Cluster plot of relative level of gene expression induction [range = 0-4x vehicle treated]
17. Induction of CYP3A4 gene expression and activity in RIF treated human hepatocytes
9
8
7
6
5
4
7.8
3
2
2.4 2.3
1
0
DTEx QPCR P450-Glo
18. Induction of CYP3A4 gene expression and activity in RIF treated HepaRG cells
5
4.5
4
3.5
3
2.5
4.5
4.1
2
1.5
1
1.8
0.5
0
DTEx QPCR P450-Glo
19. DTExtm Gene Expression Analysis
All DTExtm genes are involved in drug metabolism, conjugation or transport
* interrogate for both known and unknown drug effects on gene expression
** CYP3A4 induction by RIF (PXR mediated effects on ABCB1 & UGT1A1)
** different levels of CYP3A4 gene expression and induction in different donors
** CYP1A2 induction by BNF (AHR mediated effects on ABCC2 & UGT1A1)
** RIF (PXR) effects on SULT1A1, 1E1, 2A1, UGT2B, ABCA9, A13 and C13 gene expression and activity?
All DTExtm genes are members of coordinate regulatory pathways
* internal control for induction or suppression of gene expression
** coordinate regulation of CYP3A4, UGT1A1 and ABCB1 via PXR activation by RIF
** coordinate regulation of CYP1A2, UGT1A1 and ABCC2 via AHR activation by BNF
* control for drug selectivity or specificity in the modulation of gene expression
* concordance between DTExtm microarray, Q-PCR and functional activity assays for CYP induction studies
DTExtm microarray analysis is reliable and reproducible
* either biological replicates or experimental replicates