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Littérature scientifique sur le sujet « KDMs »

Auteur : Grafiati

Publié le 10 mars 2023

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Articles de revues sur le sujet "KDMs"

Dorna, Dawid, et Jarosław Paluszczak. « The Emerging Significance of Histone Lysine Demethylases as Prognostic Markers and Therapeutic Targets in Head and Neck Cancers ». Cells 11, n^o 6 (17 mars 2022) : 1023. http://dx.doi.org/10.3390/cells11061023.

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Epigenetic aberrations, associated with altered DNA methylation profiles and global changes in the level of histone modifications, are commonly detected in head and neck squamous cell carcinomas (HNSCC). Recently, histone lysine demethylases have been implicated in the pathogenesis of HNSCC and emerged as potential molecular targets. Histone lysine demethylases (KDMs) catalyze the removal of methyl groups from lysine residues in histones. By affecting the methylation of H3K4, H3K9, H3K27, or H3K36, these enzymes take part in transcriptional regulation, which may result in changes in the level of expression of tumor suppressor genes and protooncogenes. KDMs are involved in many biological processes, including cell cycle control, senescence, DNA damage response, and heterochromatin formation. They are also important regulators of pluripotency. The overexpression of most KDMs has been observed in HNSCC, and their inhibition affects cell proliferation, apoptosis, cell motility, invasiveness, and stemness. Of all KDMs, KDM1, KDM4, KDM5, and KDM6 proteins are currently regarded as the most promising prognostic and therapeutic targets in head and neck cancers. The aim of this review is to present up-to-date knowledge on the significance of histone lysine demethylases in head and neck carcinogenesis and to discuss the possibility of using them as prognostic markers and pharmacological targets in patients’ treatment.

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Vicioso-Mantis, Marta, Samuel Aguirre et Marian A. Martínez-Balbás. « JmjC Family of Histone Demethylases Form Nuclear Condensates ». International Journal of Molecular Sciences 23, n^o 14 (11 juillet 2022) : 7664. http://dx.doi.org/10.3390/ijms23147664.

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The Jumonji-C (JmjC) family of lysine demethylases (KDMs) (JMJC-KDMs) plays an essential role in controlling gene expression and chromatin structure. In most cases, their function has been attributed to the demethylase activity. However, accumulating evidence demonstrates that these proteins play roles distinct from histone demethylation. This raises the possibility that they might share domains that contribute to their functional outcome. Here, we show that the JMJC-KDMs contain low-complexity domains and intrinsically disordered regions (IDR), which in some cases reached 70% of the protein. Our data revealed that plant homeodomain finger protein (PHF2), KDM2A, and KDM4B cluster by phase separation. Moreover, our molecular analysis implies that PHF2 IDR contributes to transcription regulation. These data suggest that clustering via phase separation is a common feature that JMJC-KDMs utilize to facilitate their functional responses. Our study uncovers a novel potential function for the JMJC-KDM family that sheds light on the mechanisms to achieve the competent concentration of molecules in time and space within the cell nucleus.

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Wigle, Tim J., Kerren K. Swinger, John E. Campbell, Michael D. Scholle, John Sherrill, Elizabeth A. Admirand, P. Ann Boriack-Sjodin et al. « A High-Throughput Mass Spectrometry Assay Coupled with Redox Activity Testing Reduces Artifacts and False Positives in Lysine Demethylase Screening ». Journal of Biomolecular Screening 20, n^o 6 (9 mars 2015) : 810–20. http://dx.doi.org/10.1177/1087057115575689.

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Demethylation of histones by lysine demethylases (KDMs) plays a critical role in controlling gene transcription. Aberrant demethylation may play a causal role in diseases such as cancer. Despite the biological significance of these enzymes, there are limited assay technologies for study of KDMs and few quality chemical probes available to interrogate their biology. In this report, we demonstrate the utility of self-assembled monolayer desorption/ionization (SAMDI) mass spectrometry for the investigation of quantitative KDM enzyme kinetics and for high-throughput screening for KDM inhibitors. SAMDI can be performed in 384-well format and rapidly allows reaction components to be purified prior to injection into a mass spectrometer, without a throughput-limiting liquid chromatography step. We developed sensitive and robust assays for KDM1A (LSD1, AOF2) and KDM4C (JMJD2C, GASC1) and screened 13,824 compounds against each enzyme. Hits were rapidly triaged using a redox assay to identify compounds that interfered with the catalytic oxidation chemistry used by the KDMs for the demethylation reaction. We find that overall this high-throughput mass spectrometry platform coupled with the elimination of redox active compounds leads to a hit rate that is manageable for follow-up work.

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Bonnici, Joanna, Anthony Tumber, Akane Kawamura et Christopher J. Schofield. « Inhibitors of both the N -methyl lysyl- and arginyl-demethylase activities of the JmjC oxygenases ». Philosophical Transactions of the Royal Society B : Biological Sciences 373, n^o 1748 (23 avril 2018) : 20170071. http://dx.doi.org/10.1098/rstb.2017.0071.

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The Jumonji C (JmjC) family of 2-oxoglutarate (2OG)-dependent oxygenases have established roles in the regulation of transcription via the catalysis of demethylation of N ε - methylated lysine residues in histone tails, especially the N - terminal tail of histone H3. Most human JmjC N ɛ -methyl lysine demethylases (KDMs) are complex enzymes, with ‘reader domains’ in addition to their catalytic domains. Recent biochemical evidence has shown that some, but not all, JmjC KDMs also have N ω - methyl arginyl demethylase (RDM) activity. JmjC KDM activity has been linked to multiple cancers and some JmjC proteins are therapeutic targets. It is, therefore, important to test not only whether compounds in development inhibit the KDM activity of targeted JmjC demethylases, but also whether they inhibit other activities of these proteins. Here we report biochemical studies on the potential dual inhibition of JmjC KDM and RDM activities using a model JmjC demethylase, KDM4E (JMJD2E). The results reveal that all of the tested compounds inhibit both the KDM and RDM activities, raising questions about the in vivo effects of the inhibitors. This article is part of a discussion meeting issue ‘Frontiers in epigenetic chemical biology’.

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Kim, Yoon-Jung, Dong Hoon Lee, Yong-Sung Choi, Jin-Hyun Jeong et So Hee Kwon. « Benzo[b]tellurophenes as a Potential Histone H3 Lysine 9 Demethylase (KDM4) Inhibitor ». International Journal of Molecular Sciences 20, n^o 23 (25 novembre 2019) : 5908. http://dx.doi.org/10.3390/ijms20235908.

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Gene expression and tumor growth can be regulated by methylation levels of lysine residues on histones, which are controlled by histone lysine demethylases (KDMs). Series of benzo[b]tellurophene and benzo[b]selenophene compounds were designed and synthesized and they were evaluated for histone H3 lysine 9 demethylase (KDM4) inhibitory activity. Among the carbamates, alcohol and aromatic derivatives, tert-butyl benzo[b]tellurophen-2-ylmethylcarbamate (compound 1c) revealed KDM4 specific inhibitory activity in cervical cancer HeLa cells, whereas the corresponding selenium or oxygen substitute compounds did not display any inhibitory activity toward KDM4. Compound 1c also induced cell death in cervical and colon cancer but not in normal cells. Thus, compound 1c, a novel inhibitor of KDM4, constitutes a potential therapeutic and research tool against cancer.

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Guo, Xiaoqiang, et Qiaoxia Zhang. « The emerging role of histone demethylases in renal cell carcinoma ». Journal of Kidney Cancer and VHL 4, n^o 2 (2 mai 2017) : 1–5. http://dx.doi.org/10.15586/jkcvhl.2017.56.

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Renal cell carcinoma (RCC), the most common kidney cancer, is responsible for more than 100,000 deaths per year worldwide. The molecular mechanism of RCC is poorly understood. Many studies have indicated that epigenetic changes such as DNA methylation, noncoding RNAs, and histone modifications are central to the pathogenesis of cancer. Histone demethylases (KDMs) play a central role in histone modifications. There is emerging evidence that KDMs such as KDM3A, KDM5C, KDM6A, and KDM6B play important roles in RCC. The available literature suggests that KDMs could promote RCC development and progression via hypoxia-mediated angiogenesis pathways. Small-molecule inhibitors of KDMs are being developed and used in preclinical studies; however, their clinical relevance is yet to be established. In this mini review, we summarize our current knowledge on the putative role of histone demethylases in RCC.

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Wang, Zhanxin, et Dinshaw J. Patel. « Small molecule epigenetic inhibitors targeted to histone lysine methyltransferases and demethylases ». Quarterly Reviews of Biophysics 46, n^o 4 (2 septembre 2013) : 349–73. http://dx.doi.org/10.1017/s0033583513000085.

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AbstractAltered chromatin structures and dynamics are responsible for a range of human malignancies, among which the status of histone lysine methylation remains of paramount importance. Histone lysine methylation is maintained by the relative activities of sequence-specific methyltransferase (KMT) writers and demethylase (KDM) erasers, with aberrant enzymatic activities or expression profiles closely correlated with multiple human diseases. Hence, targeting these epigenetic enzymes should provide a promising avenue for pharmacological intervention of aberrantly marked sites within the epigenome. Here we present an up-to-date critical evaluation on the development and optimization of potent small molecule inhibitors targeted to histone KMTs and KDMs, with the emphasis on contributions of structural biology to development of epigenetic drugs for therapeutic intervention. We anticipate that ongoing advances in the development of epigenetic inhibitors should lead to novel drugs that site-specifically target KMTs and KDMs, key enzymes responsible for maintenance of the lysine methylation landscape in the epigenome.

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Nic-Can, Geovanny I., Beatriz A. Rodas-Junco, Leydi M. Carrillo-Cocom, Alejandro Zepeda-Pedreguera, Ricardo Peñaloza-Cuevas, Fernando J. Aguilar-Ayala et Rafael A. Rojas-Herrera. « Epigenetic Regulation of Adipogenic Differentiation by Histone Lysine Demethylation ». International Journal of Molecular Sciences 20, n^o 16 (12 août 2019) : 3918. http://dx.doi.org/10.3390/ijms20163918.

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Obesity is a rising public health problem that contributes to the development of several metabolic diseases and cancer. Adipocyte precursors outside of adipose depots that expand due to overweight and obesity may have a negative impact on human health. Determining how progenitor cells acquire a preadipocyte commitment and become mature adipocytes remains a significant challenge. Over the past several years, we have learned that the establishment of cellular identity is widely influenced by changes in histone marks, which in turn modulate chromatin structure. In this regard, histone lysine demethylases (KDMs) are now emerging as key players that shape chromatin through their ability to demethylate almost all major histone methylation sites. Recent research has shown that KDMs orchestrate the chromatin landscape, which mediates the activation of adipocyte-specific genes. In addition, KDMs have functions in addition to their enzymatic activity, which are beginning to be revealed, and their dysregulation seems to be related to the development of metabolic disorders. In this review, we highlight the biological functions of KDMs that contribute to the establishment of a permissive or repressive chromatin environment during the mesenchymal stem cell transition into adipocytes. Understanding how KDMs regulate adipogenesis might prompt the development of new strategies for fighting obesity-related diseases.

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Nanduri, Jayasri, Ning Wang, Benjamin L. Wang et Nanduri R. Prabhakar. « Lysine demethylase KDM6B regulates HIF-1α-mediated systemic and cellular responses to intermittent hypoxia ». Physiological Genomics 53, n^o 9 (1 septembre 2021) : 385–94. http://dx.doi.org/10.1152/physiolgenomics.00045.2021.

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Intermittent hypoxia (IH) is a hallmark manifestation of obstructive sleep apnea (OSA). Rodents treated with IH exhibit hypertension. Hypoxia-inducible factor (HIF)-1-dependent transcriptional activation of NADPH oxidases ( Nox) and the resulting increase in reactive oxygen species (ROS) levels is a major molecular mechanism underlying IH/OSA-induced hypertension. Jumanji C (JmjC)-containing histone lysine demethylases (JmjC-KDMs) are coactivators of HIF-1-dependent transcriptional activation. In the present study, we tested the hypothesis that JmjC-KDMs are required for IH-evoked HIF-1 transcriptional activation of Nox4 and the ensuing hypertension. Studies were performed on pheochromocytoma (PC)12 cells and rats. IH increased KDM6B protein and enzyme activity in PC12 cells in an HIF-1-independent manner as evidenced by unaltered KDM6B activation by IH in HIF-1α shRNA-treated cells. Cells treated with IH showed increased HIF-1-dependent Nox4 transcription as indicated by increased HIF-1α binding to hypoxia-responsive element (HRE) sequence of the Nox4 gene promoter demonstrated by chromatin immunoprecipitation (ChiP) assay. Pharmacological blockade of KDM6B with GSKJ4, a specific KDM6 inhibitor, or genetic silencing of KDM6B with shRNA abolished IH-induced Nox4 transcriptional activation by blocking HIF-1α binding to the promoter of the Nox4 gene. Treating IH-exposed rats with GSKJ4 showed: 1) absence of KDM6B activation and HIF-1-dependent Nox4 transcription in the adrenal medullae, and 2) absence of elevated plasma catecholamines and hypertension. Collectively, these findings indicate that KDM6B functions as a coactivator of HIF-1-mediated Nox4 transactivation and demonstrates a hitherto uncharacterized role for KDMs in IH-induced hypertension by HIF-1.

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Karásek, Matej, et Ľubica Kollárová. « The Christian Democratic Youth of Slovakia : Christian Legacy, Post-Socialist Memory and the Present Spirit of Capitalism ». Ethnologia Actualis 15, n^o 1 (1 juin 2015) : 40–64. http://dx.doi.org/10.1515/eas-2015-0008.

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Abstract The subject of this case study is the youth political organisation Christian Democratic Youth of Slovakia (KDMS). The first parts of this paper are dedicated to history and the structure of organisation. Latter parts discuss the influence of historical memory on creating the collective discourses of KDMS and its civic engagements, ambitions and activities. The purpose of the paper is also to evaluate the role of religion and secularisation in KDMS agenda and also to discuss the ways how the ´christian heritage´ becames the source for arguments in political debates and opossitely how the christianity could be interpreted in the light of conservative and right oriented socio-economic and political worldview.

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Thèses sur le sujet "KDMs"

Balzano, Amodio Luca. « Design, synthesis, biological evaluation and binding studies of new small-molecule modulators of KDMs (lysine-specific demethylases) ». Doctoral thesis, Universita degli studi di Salerno, 2017. http://hdl.handle.net/10556/2419.

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2014 - 2015
JHDMs (JmjC-domain-containing histone demethylases) are the largest class of demethylase enzymes, contain a Jumonji C (JmjC) domain and catalyze lysine demethylation of histones through an oxidative reaction that requires Fe(II) ion and α-ketoglutarate (2OG) as cofactors. The misregulation of these enzymes, in particular JMJD2 subfamily, has being significantly implicated in cancer initiation and progression. Potent and specific inhibitors of these enzymes have not been identified yet, most of them inhibiting many other Fe(II)/2OG dependent oxygenases or being affected by undesirable characteristics. Here, we describe the discovery by high throughput screening (HTS) of a bunch of novel hit compounds active against KDM4s and the subsequent hit validation stage to select the most interesting ones for further derivatization. The use of a multiple combined approach of different in vitro techniques led us to select the hit EML586 as starting point for the development of novel optimized derivatives. The substitution of quinoxaline ring with more aliphatic portions gave derivatives such as EML678 and EML684, which demonstrate a better activity against hKDM4A compared to the starting hit compound. Furthermore, they induced a marked reduction in methylation of lysines H3K9 and H3K27 in a cell-based assay together with a marked arrest in the S phase of cell cycle. [edited by author]
Le JHDM (demetilasi istoniche contenenti il dominio JmjC) rappresentano la più numerosa classe di enzimi ad attività demetilasica, contengono il dominio Jumonji C (JmjC) e tramite esso sono in grado di catalizzare la rimozione del gruppo metile da residui di lisina istonici tramite una reazione ossidativa che utilizza lo ione Fe(II) e l’α-chetoglutarato (2OG) come cofattori. Un’attività aberrante di questi enzimi, in particolare della sottofamiglia JMJD2, sembra essere correlata in maniera significativa alla genesi e alla progressione di diverse forme tumorali. Non sono stati ancora identificati inibitori potenti e specifici per questa classe enzimatica, la gran parte delle molecole ad oggi note, infatti, è affetta da caratteristiche indesiderabili come scarsa permeabilità cellulare e mancanza di selettività verso gli altri enzimi Fe(II)/2OG dipendenti. In questo lavoro è descritta la scoperta tramite high throughput screening (HTS) di un gruppo di nuovi composti hit attivi contro KDM4 ed il successivo processo di validazione utilizzato per selezionare i derivati più interessanti per il futuro sviluppo. L’utilizzo di un approccio multiplo, combinato di differenti tecniche in vivo ha permesso di selezionare il composto EML586, punto di partenza per lo sviluppo di nuovi derivati ottimizzati. La sostituzione dell’anello chinossalinico con porzioni più alifatiche ha portato all’ottenimento dei derivati EML678 e EML684, che dimostrano una migliore attività inibitoria verso KDM4A umana rispetto al composto hit di partenza. Inoltre, tali derivati inducono una marcata riduzione del livello di metilazione delle lisine H3K9 e H3K27 in cellula insieme ad un evidente arresto del ciclo cellulare nella fase S. [a cura dell'autore]
XV n.s.(XXIX ciclo)

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Schiller, Rachel Shamo. « Investigating the inhibitor and substrate diversity of the JmjC histone demethylases ». Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:1e7fd2a1-a9c3-48f7-8fa7-a041299d42f9.

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Epigenetic control of gene expression by histone post-translational modifications (PTMs) is a complex process regulated by proteins that can 'read', 'write' or 'erase' these PTMs. The histone lysine demethylase (KDM) family of epigenetic enzymes remove methyl modifications from lysines on histone tails. The Jumonji C domain (JmjC) family is the largest family of KDMs. Investigating the scope and mechanisms of the JmjC KDMs is of interest for understanding the diverse functions of the JmjC KDMs in vivo, as well as for the application of the basic science to medicinal chemistry design. The work described in this thesis aimed to biochemically investigate the inhibitor and substrate diversity of the JmjC KDMs, it led to the identification of new inhibitors and substrates and revealed a potential combinatorial dependence between adjacent histone PTMs. Structure-activity relationship studies gave rise to an n-octyl ester form of IOX1 with improved cellular potency and selectivity towards the KDM4 subfamily. This compound should find utility as a basis for the development of JmjC inhibitors and as a tool compound for biological studies. The rest of this thesis focused on the biochemical investigations of potential substrates and inhibitors for KDM3A, a JmjC demethylase with varied physiological functions. Kinetic characterisation of reported KDM3A substrates was used as the basis for evaluations of novel substrates and inhibitors. Further studies found TCA cycle intermediates to be moderate co-substrate competitive inhibitors of KDM3A. Biochemical investigations were carried out to study potential protein-protein interactions of KDM3A with intraflagellar transport proteins (IFTs), non-histone proteins involved in the formation of sperm flagellum. Work then addressed the exploration of novel in vitro substrates for KDM3 (KDM3A and JMJD1C) mediated catalysis, including: methylated arginines, lysine analogues, acetylated and formylated lysines. KDM3A, and other JmjC KDMs, were found to catalyse novel arginine demethylation reaction in vitro. Knowledge gained from studies with unnatural lysine analogues was utilised to search for additional novel PTM substrates for KDM3A. These results constitute the first evidence of JmjC KDM catalysed hydroxylation of an Nε-acetyllysine residue. The H3 K4me3 position seems to be required for acetyllysine substrate recognition, implying a combinatorial effect between PTMs. Preliminary results provide evidence that JMJD1C, a KDM3 protein previously reported to be inactive, may catalyse deacetylation in vitro. An additional novel reaction, observed with both KDM3A and JMJD1C, is deformylation of N^ε-formyllysine residues on histone H3 fragment peptides. Interestingly, H3 K4 methylation was also observed to enhance the apparent deformylation of both KDM3A and JMJD1C catalysed reactions. Overall, findings in this thesis suggest that the catalytic activity of JmjC KDMs extends beyond lysine demethylation. In a cellular context, members of the KDM3 subfamily might provide a regulatory link between methylation and acylation marks. Such a link will further highlight the complex relationships between histone PTMs and the epigenetic enzymes that regulate them. The observed dependency of H3 K9 catalysis on H3 K4 methylation adds another layer of complexity to the epigenetic regulation by histone PTMs.

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Hookway, Edward. « The role of the lysine demethylases KDM5 and KDM6 in bone malignancies ». Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:b591861f-985b-4722-8027-492e750f3ff7.

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Methylation of histone lysine residues functions as a dynamic, reversible mechanism for regulating gene expression and aberrations in this process have been linked with the development of cancer. Members of the lysine demethylase (KDM) family remove methyl marks from histones. KDM5B removes methyl marks from histone H3 lysine 4 (H3K4) whereas KDM6A and KDM6B remove methyl marks from histone H3 lysine 27 (H3K27). In this thesis, GSK-J4, an inhibitor of KDM5B, KDM6A and KDM6B, is shown to impair viability in a range of cancers affecting bone including multiple myeloma, Ewing sarcoma and chordoma. GSK-J4 induces a biphasic transcriptional response, characterized by an early, massive rise in the expression of a number of cysteine-rich metallothionein genes followed by induction of ATF4 via phosphorylation of eIF2Î± by GCN2. Induction of ATF4 leads to apoptosis in myeloma cells and cell cycle arrest in Ewing sarcoma. Ectopic overexpression of metallothioneins is shown to be sufficient to induce the ATF4 response. GSK-J4 is shown to alters cellular metabolism by impairing glutaminolysis. ChIPseq demonstrates a global increased H3K27me3 in response to treatment with GSK-J4 with a decrease in H3K4me3 around transcription start sites of genes not involved in the ATF4 response. Combined knockdown of KDM6A and KDM6B recapitulates the cellular response to GSK-J4 whereas inhibition of KDM5B is not sufficient to reproduce the effect. A model is presented suggesting that the increased requirement for incorporation of cysteine into protein due to the expression of metallothioneins leads to the presence of uncharged cysteinyl-tRNA molecules that are sensed by GCN2 leading to activation of an ATF4-driven integrated stress response.

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Chen, Runqiu, et 陳潤球. « Statistical validation of kidney deficiency syndromes (KDS) and the development of a KDS questionnaire in Hong Kong Chinese women aged 40-60 years ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B43223813.

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Chen, Runqiu. « Statistical validation of kidney deficiency syndromes (KDS) and the development of a KDS questionnaire in Hong Kong Chinese women aged 40-60 years ». Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B43223813.

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Ådahl, Hanna, et My Brännström. « The naked truth ? : En kritisk diskursanalys om fast fashion-företaget NA-KD:s externa kommunikation ». Thesis, Umeå universitet, Institutionen för kultur- och medievetenskaper, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-179312.

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The purpose of this study was to increase the understanding of how the Swedish fast fashion company NA-KD expressed its profile and how it could be linked to sustainability. The fashion industry is known for having big sustainability problems, and that is why the main focus of this study was the paradox between fast fashion and sustainability due to its conflict nature. To concretise the aim of the study, we formulated two questions: “What discourses can be found in NA-KD’s external communication?” and “What profile does the company express through their website?”. To analyse the company’s website we included relevant theories about the individualised consumer society, sustainable consumption and marketing communication. The used method for this study was Fairclough’s critical discourse analysis, which was a useful method to enable a critical perspective. Fairclough’s approach made it possible to examine how, and in what way, NA-KD expressed their external communication. The material consisted of ten texts found on the company’s website that were analysed closely and resulted in a number of findings. We found three discourses: the business discourse, the consumer discourse and the sustainability discourse. Those helped us to increase the understanding of the company’s profile, since we discovered a range of different tendencies. The main ones were that NA-KD constructed truth, encouraged more consumption, built relations with the consumer and expressed values and responsibility about sustainability. With those in mind, we concluded that it is doubtful that NA-KD’s sustainability communication is completely honest. They encouraged the consumer to buy more fast fashion clothing, which affects the environment negatively, at the same time as they communicated consciousness about the fashion industry’s impact on the environment. We also found that the communication was contradictory and misleading, hence that some information about their sustainability work does not comply with what is presented. Our main conclusion is therefore that NA-KD’s profile is ambiguous and difficult to establish.

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Khin, Khin Nyo Aree Jampaklay. « Access to health utilization among people aged 50 and older in KDSS is it equal / ». Abstract, 2007. http://mulinet3.li.mahidol.ac.th/thesis/2550/cd404/4938533.pdf.

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Bader, Caroline, Eva-Louise Castefelt et Louise Gunnarsson. « Influencers Marketing : En fallstudie om NA-KDs nyckel till en god tillväxt ». Thesis, Högskolan i Borås, Akademin för textil, teknik och ekonomi, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:hb:diva-15381.

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Begreppet influencer blir mer och mer välkänt för varje dag. Begreppet syftar till ett yrke som vuxit fram i takt med internet. Även om det finns mycket information att tillgå kring fenomenet finns det många aspekter som fortfarande icke blivit belysta. Den information som finns att tillgå kring ämnet är inte heller i vetenskaplig tappning. Syftet med studien är att analysera och redogöra för hur influencer marketing kan påverka tillväxten för ett företag. Härtill studeras influencers inverkan på varumärkesbyggandet i relation till tillväxt. Följande kommer en fallstudie i samarbete med klädföretaget NA-KD presenteras. NA-KDs snabba tillväxt kommer förklaras med lämpligt teoretiska underlag och inte minst av medgrundaren själv. Det moderna sättet att marknadsföra via sociala medier med influencers kommer vidare att undersökas i ljuset av olika aspekter. Hur ett samarbete med en eller flera influencers ser ut kommer att undersökas med koppling till hur strategin har hjälpt NA-KD att växa under kort tid. Varumärkesutveckling och teorier kring ett företags tillväxt är två andra viktiga områden som kommer att studeras för att uppsatsen ska få en relevant och genomtänkt slutsats. Alla presenterade teorier kommer att kopplas till NA-KDs egna tillväxt. Metoden vald för följande uppsats är av den kvalitativa typen. Empiriinsamlingen kommer att bestå av en intervju med en medgrundare i fallföretaget, NA-KD. Vidare kommer företagets hemsida och Instagramkonton observeras, likaså kommer fyra utvalda influencers konton observeras. Även sekundär data så som NA-KDs årsredovisning samt en överskådlig presentation av ett par konkurrenter läggs fram. Efter analys av empirin trädde tydliga slutsatser fram. Kopplingar mellan influencer marketing och tillväxt blev ett klart faktum. Likaså blev samarbetet mellan företaget och person förtydligat. Det stod även klart att NA-KD ligger rätt i tiden och grundades när influencers redan vuxit fram och fått en stor inverkan.
The term influencer is becoming more and more known for each day. The term aims at a profession that has emerged in line with the internet. Although there is much information available about the phenomenon, there are many aspects that have not yet been illuminated. The information available on the subject is also not of scientific sort. The purpose of the study is to analyze and explain how influencer marketing can affect the growth of a company. In addition, influencers affect the brand building. Following thesis will consist of a case study in collaboration with the clothing company NA- KD. The rapid growth of NA-KD will be explained by appropriate theoretical evidence, and not least by the co-founder himself. The modern way of marketing through social media with influencers will be investigated in light of various aspects. How cooperation with one or more influencers looks will be investigated in conjunction with how the strategy has helped NA-KD grow in a short period of time. Brand development and theories about a company's growth are two other important areas that will be studied in order for the thesis to have a relevant and well-reasoned conclusion. All theories presented will be linked to NA-KD’s own growth. The method chosen for the following thesis is of the qualitative type. The empirical collection will consist of an interview with a co-founder of the chosen company, NA-KD. Furthermore, the company's website and Instagram accounts will be observed, as well as four selected influencer's accounts that will also be observed. As well as secondary data such as the NA-KD annual report and a review of a few competitors will be presented. After analysis of the empiric data, clear conclusions emerged. Linkages between influencer marketing and growth became a clear fact. Likewise, cooperation between the companies and individuals was clarified. It was also clear that NA-KD was founded when influencers had already grown and had a major impact. Following thesis will be in Swedish.

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Tingare, Asmita. « The role of the KDM4 family histone 3 lysine 9 demethylases in hypertrophic remodelling of cardiac myocytes ». Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648522.

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Santos, Bruno Marinho. « Extensões do metamodelo KDM para apoiar modernizações orientadas a aspectos de sistemas legados ». Universidade Federal de São Carlos, 2014. https://repositorio.ufscar.br/handle/ufscar/593.

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Maintaining legacy systems is a complex and expensive activity for many companies. A recently proposal to solve this problem is Architecture-Driven Modernization (ADM), proposed by Object Management Group (OMG). The ADM consists of a set of concepts and standard metamodels that support systems modernization using models. The Knowledge Discovery Metamodel (KDM) is the main metamodel of ADM, it can represent many artifacts of a legacy system, such as source code, architecture, user interface, configuration files and business process. In general, legacy systems have crosscutting concerns, it can show source code problems like tangling and scattering, and it raises the maintenance costs. The aspect orientation is an alternative to improve crosscutting concerns modularization. Thus, in this dissertation is presented the term Aspect Oriented Modernization that uses the aspect oriented concepts in the ADM context. This modernization process consists in modularize legacy systems with aspects represented in model level. To achieve this goal, in this work were performed a lightweight and a heavyweight extension in the KDM metamodel, to analyze which one would present a better performance if used by Modernization Engineers. The evaluation of these extensions was performed by a case study that considered the modernization with aspects of a small-sized system. To evaluate the case study in both extensions, a set of comparison criteria were created to support the software engineers in choosing the best extension mechanism, according to their needs. In the context of this dissertation an experimental study were developed that aimed reproducing the scenarios that the modernization engineers had to perform maintenances and developing new refactorings in a aspect oriented KDM model. The experiment data considered the development time of the activities and the found number of errors. Finally, it was noticed that the extension mechanism to be choose will depend on the context that it will be applied, however, considering the approach studied here the best extension mechanism is the heavyweight one.
Manter sistemas legados é uma atividade complexa e onerosa para muitas empresas. Uma proposta recente para esse problema é a Modernização Dirigida à Arquitetura (Architecture-Driven Modernization - ADM), proposta pela OMG (Object Management Group). A ADM consiste em um conjunto de princípios e metamodelos padrões que apoiam a modernização de sistemas utilizando modelos. O Knowledge Discovery Metamodel (KDM) é o principal metamodelo da ADM, podendo representar diversos artefatos de um sistema, como código-fonte, arquitetura, interface de usuário, arquivos de configuração e processos de negócio. Em geral, sistemas legados possuem interesses transversais, apresentando problemas de entrelaçamento e espalhamento de código, o que eleva os custos de manutenção. A orientação a aspectos é uma alternativa para melhorar a modularização de interesses transversais. Mediante isso, neste trabalho é apresentado o termo Modernização Orientada a Aspectos que utiliza os conceitos da orientação a aspectos na ADM. Essa modernização consiste em remodularizar sistemas legados utilizando aspectos representados em nível de modelo. Para atingir esse objetivo, foi realizada uma extensão leve e outra pesada do metamodelo KDM, para analisar em qual das duas o desempenho dos engenheiros de modernização seria melhor. Para fazer a avaliação das extensões, foi realizado um estudo de caso levando em consideração a modernização com aspectos em um sistema de pequeno porte. Com o objetivo de avaliar o estudo de caso usando as duas extensões, foram desenvolvidos critérios de comparação que auxiliassem os engenheiros de software a escolher qual dos dois mecanismos de extensão utilizar em seu projeto. Foi feito também um estudo experimental que buscou reproduzir os cenários em que engenheiros de modernização tivessem que realizar manutenções e desenvolver novas refatorações em um modelo KDM orientado a aspectos. Os dados do experimento foram avaliados em relação ao tempo de desenvolvimento das atividades e quantidade de erros encontrados. Por fim, percebeu-se que o mecanismo de extensão a ser utilizado vai depender do contexto em que ele será aplicado, mas, para o domínio aqui estudado a extensão que melhor atendeu aos requisitos foi a pesada.

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Plus de sources

Livres sur le sujet "KDMs"

Solakov, Angel. Predsedateli͡a︡t na KDS razkazva--. Sofii͡a︡ : "Teksimreklama" AD, 1993.

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Ze studně večera kdos něžný vážil krev. Boskovice : Albert, 2009.

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Nussbaum, Debra. KDES curriculum guide for auditory and speech training. 2^e éd. Washington, DC : Pre-College Programs, Gallaudet University, 1988.

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Sanders, Addie Meyer. Alligators under the bed : PMZ 4 KDS. [Sayville, N.Y.] (3 Mill Pond Rd., Sayville 11782) : [Sanders, 1990.

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Kitingan, Jeffrey G. Masa depan masyarakat Kadazandusun dan Murut (KDM) : Kemanakah arah kita dari sini ? Kota Kinabalu, Sabah, Malaysia : Koisaan Cultural Development Institute, 1997.

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Kristen demokrati på svenska : Studier om KDS tillkomst och utveckling 1964-1982. Lund : CWK Gleerup, 1985.

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Kyritz, Heinz. Wenn Ein Engel Kdme. Authorhouse, 2004.

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Giblin, James Cross, et Eileen Christelow. JEROME+WITCHCRAFT KDS PA. Clarion Books, 1990.

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Kūle, Maija, dir. Kritiskā domāšana : izglītība, medijpratība, spriestspēja. LU Filozofijas un socioloģijas institūts, 2018. http://dx.doi.org/10.22364/kdims.

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Staff, Thomas Nelson Publishing. Great Sngs Chrsitms and Kds. Nelson Incorporated, Thomas, 1994.

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Plus de sources

Chapitres de livres sur le sujet "KDMs"

McLaughlin-Drubin, Margaret. « KDM6 ». Dans Encyclopedia of Cancer, 1–3. Berlin, Heidelberg : Springer Berlin Heidelberg, 2014. http://dx.doi.org/10.1007/978-3-642-27841-9_7177-3.

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McLaughlin-Drubin, Margaret. « KDM6 ». Dans Encyclopedia of Cancer, 2391–93. Berlin, Heidelberg : Springer Berlin Heidelberg, 2017. http://dx.doi.org/10.1007/978-3-662-46875-3_7177.

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Knechtli, Hanspeter. « Kantonale Drucksachen- und Materialzentrale Zürich (kdmz) ». Dans E-Business-Integration, 53–66. München : Carl Hanser Verlag GmbH & Co. KG, 2003. http://dx.doi.org/10.3139/9783446226432.004.

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Naor, Moni, Benny Pinkas et Omer Reingold. « Distributed Pseudo-random Functions and KDCs ». Dans Advances in Cryptology — EUROCRYPT ’99, 327–46. Berlin, Heidelberg : Springer Berlin Heidelberg, 1999. http://dx.doi.org/10.1007/3-540-48910-x_23.

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Gaži, Peter, et Stefano Tessaro. « Provably Robust Sponge-Based PRNGs and KDFs ». Dans Advances in Cryptology – EUROCRYPT 2016, 87–116. Berlin, Heidelberg : Springer Berlin Heidelberg, 2016. http://dx.doi.org/10.1007/978-3-662-49890-3_4.

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Davies, Gareth T., et Martijn Stam. « KDM Security in the Hybrid Framework ». Dans Topics in Cryptology – CT-RSA 2014, 461–80. Cham : Springer International Publishing, 2014. http://dx.doi.org/10.1007/978-3-319-04852-9_24.

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Chang, Jinyong, Honglong Dai et Maozhi Xu. « The KDM-CCA Security of REACT ». Dans Information Security Practice and Experience, 85–101. Cham : Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-72359-4_5.

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Groffmann, Hans-Dieter. « Kennzahlendatenmodell (KDM) als Grundlage aktiver Führungsinformationssysteme ». Dans Daten- und Funktionsmodellierung, 1–29. Wiesbaden : Gabler Verlag, 1992. http://dx.doi.org/10.1007/978-3-322-85475-9_1.

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Groffmann, Hans-Dieter. « Kennzahlendatenmodell (KDM) als Grundlage aktiver Führungsinformationssysteme ». Dans DGOR / ÖGOR, 488. Berlin, Heidelberg : Springer Berlin Heidelberg, 1993. http://dx.doi.org/10.1007/978-3-642-78196-4_135.

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Marcedone, Antonio, Rafael Pass et Abhi Shelat. « Bounded KDM Security from iO and OWF ». Dans Lecture Notes in Computer Science, 571–86. Cham : Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-44618-9_30.

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Actes de conférences sur le sujet "KDMs"

TSENG, CHIA YAN, SHIA CHUNG CHEN, WEN REN JONG et YUNG HSIANG CHANG. « Knowledge Based Deriven Manufacturing System KDMS for Injection Molding ». Dans Second International Conference on Advances in Mechanical and Automation Engineering - MAE 2015. Institute of Research Engineers and Doctors, 2015. http://dx.doi.org/10.15224/978-1-63248-045-3-40.

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Lee, Tai Sik, Dong Wook Lee et Sang Bok Jee. « Development of Knowledge Document Management System (KDMS) for Sharing Construction Technical Documents ». Dans Construction Research Congress 2005. Reston, VA : American Society of Civil Engineers, 2005. http://dx.doi.org/10.1061/40754(183)115.

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Khalefa, Mohamed E., et Sameh S. El-Atawy. « Demonstrating KDBMS ». Dans SSDBM '16 : Conference on Scientific and Statistical Database Management. New York, NY, USA : ACM, 2016. http://dx.doi.org/10.1145/2949689.2949714.

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Ohanian, Vigen, Thomas M. Snyder et Ananda Gunawardena. « Analytic properties of thef‐kDMO operator ». Dans SEG Technical Program Expanded Abstracts 1993. Society of Exploration Geophysicists, 1993. http://dx.doi.org/10.1190/1.1822315.

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Yi Yang, Tao Zheng et Xin Lin. « A KDSS for green dyeing and printing management ». Dans 2010 International Conference on Computer Design and Applications (ICCDA 2010). IEEE, 2010. http://dx.doi.org/10.1109/iccda.2010.5541512.

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Pérez-Castillo, Ricardo, Ignacio García-Rodríguez de Guzmán, Mario Piattini et Barbara Weber. « Integrating event logs into KDM repositories ». Dans the 27th Annual ACM Symposium. New York, New York, USA : ACM Press, 2012. http://dx.doi.org/10.1145/2245276.2231949.

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Kadar, Manuella, et Adrian Tulbure. « An automated knowledge discovery framework with multi-agent systems — KDMAS ». Dans 2017 International Conference on Engineering, Technology and Innovation (ICE/ITMC). IEEE, 2017. http://dx.doi.org/10.1109/ice.2017.8280025.

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Maurer, Jochen. « Abstract 155 : KDM4 inhibition targets breast cancer stem-like cells ». Dans Proceedings : AACR Annual Meeting 2018 ; April 14-18, 2018 ; Chicago, IL. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1538-7445.am2018-155.

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Ding, Yi, Weipeng Lai, Zhaoni Liu, Ming Zhao, Sihai Zhang et Shengli Zhou. « Implementation of KDML-Based Channel Estimator on GNU Radio Platform ». Dans 2021 13th International Conference on Wireless Communications and Signal Processing (WCSP). IEEE, 2021. http://dx.doi.org/10.1109/wcsp52459.2021.9613208.

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Nguyen Phung, Hang Thu, et Nahashon Nzioka Nthenya. « Women’s Education and Empowerment : Evidence from a Reform in Kenya ». Dans 13th Women's Leadership and Empowerment Conference. Tomorrow People Organization, 2022. http://dx.doi.org/10.52987/wlec.2022.005.

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ABSTRACT This article examines the causal effects of education on women empowerment, focusing on women born between 1950 and 1980 in six waves of Kenya Demographic Health Survey (KDHS) data, who were likely exposed to 1985 education policy change in Kenya. The study employs this new structuring educational system as an instrument and reported the results using reduced-form due to high repetition rate and late enrolment at that time. The findings indicate that being exposed to the new education system yields positive impact on women empowerment. Specifically, being exposed to the 8-4-4 regime, women delayed their age at first birth by approximately 0.564 years, the female genital mutilation (FGM) practice on their eldest daughters declined by 3.51%, sexual domestic violence reduced by 6.47% and their decision-making index was enhanced by 0.067 point. We also conduct some robustness checks and placebo test, and the findings are robust. We provide some potential mechanisms that experiencing the new 8-4-4 system empowers women:1) exposure to information, 2) husbands/partners’ characteristics, and 3) labour market outcome. KEYWORDS: KDHS, education, women empowerment, Kenya, gende

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