111,840 research outputs found

    How Does Reprogramming to Pluripotency Affect Genomic Imprinting?

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    Human induced Pluripotent Stem Cells (hiPSCs) have the capacity to generate a wide range of somatic cells, thus representing an ideal tool for regenerative medicine. Patient-derived hiPSCs are also used for in vitro disease modeling and drug screenings. Several studies focused on the identification of DNA mutations generated, or selected, during the derivation of hiPSCs, some of which are known to drive cancer formation. Avoiding such stable genomic aberrations is paramount for successful use of hiPSCs, but it is equally important to ensure that their epigenetic information is correct, given the critical role of epigenetics in transcriptional regulation and its involvement in a plethora of pathologic conditions. In this review we will focus on genomic imprinting, a prototypical epigenetic mechanism whereby a gene is expressed in a parent-of-origin specific manner, thanks to the differential methylation of specific DNA sequences. Conventional hiPSCs are thought to be in a pluripotent state primed for differentiation. They display a hypermethylated genome with an unexpected loss of DNA methylation at imprinted loci. Several groups recently reported the generation of hiPSCs in a more primitive developmental stage, called naïve pluripotency. Naïve hiPSCs share several features with early human embryos, such as a global genome hypomethylation, which is also accompanied by a widespread loss of DNA methylation at imprinted loci. Given that loss of imprinting has been observed in genetic developmental disorders as well as in a wide range of cancers, it is fundamental to make sure that hiPSCs do not show such epigenetic aberrations. We will discuss what specific imprinted genes, associated with human pathologies, have been found commonly misregulated in hiPSCs and suggest strategies to effectively detect and avoid such undesirable epigenetic abnormalities

    Methylated RNA immunoprecipitation assay to study m5c modification in arabidopsis

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    Secondary base modifications on RNA, such as m5C, affect the structure and function of the modified RNA molecules. Methylated RNA Immunoprecipitation and sequencing (MeRIP-seq) is a method that aims to enrich for methylated RNA and ultimately identify modified transcripts. Briefly, sonicated RNA is incubated with an antibody for 5-methylated cytosines and precipitated with the assistance of protein G beads. The enriched fragments are then sequenced and the potential methylation sites are mapped based on the distribution of the reads and peak detection. MeRIP can be applied to any organism, as it does not require any prior sequence or modifying enzyme knowledge. In addition, besides fragmentation, RNA is not subjected to any other chemical or temperature treatment. However, MeRIP-seq does not provide singlenucleotide prediction of the methylation site as other methods do, although the methylated area can be narrowed down to a few nucleotides. The use of different modification-specific antibodies allows MeRIP to be adjusted for the different base modifications present on RNA, expanding the possible applications of this method

    author-bios-SRD-19-0063.R1 – Supplemental material for The Network Structure of Police Misconduct

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    Supplemental material, author-bios-SRD-19-0063.R1 for The Network Structure of Police Misconduct by George Wood, Daria Roithmayr and Andrew V. Papachristos in Socius</p

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    BrewerIX enables allelic expression analysis of imprinted and X-linked genes from bulk and single-cell transcriptomes

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    Genomic imprinting and X chromosome inactivation (XCI) are two prototypical epigenetic mechanisms whereby a set of genes is expressed mono-allelically in order to fine-tune their expression levels. Defects in genomic imprinting have been observed in several neurodevelopmental disorders, in a wide range of tumours and in induced pluripotent stem cells (iPSCs). Single Nucleotide Variants (SNVs) are readily detectable by RNA-sequencing allowing the determination of whether imprinted or X-linked genes are aberrantly expressed from both alleles, although standardised analysis methods are still missing. We have developed a tool, named BrewerIX, that provides comprehensive information about the allelic expression of a large, manually-curated set of imprinted and X-linked genes. BrewerIX does not require programming skills, runs on a standard personal computer, and can analyze both bulk and single-cell transcriptomes of human and mouse cells directly from raw sequencing data. BrewerIX confirmed previous observations regarding the bi-allelic expression of some imprinted genes in naive pluripotent cells and extended them to preimplantation embryos. BrewerIX also identified misregulated imprinted genes in breast cancer cells and in human organoids and identified genes escaping XCI in human somatic cells. We believe BrewerIX will be useful for the study of genomic imprinting and XCI during development and reprogramming, and for detecting aberrations in cancer, iPSCs and organoids. Due to its ease of use to non-computational biologists, its implementation could become standard practice during sample assessment, thus raising the robustness and reproducibility of future studies

    Využití sociálních médií v B2B prodeji

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    Tato diplomová práce se zabývá tím, jak mohou B2B obchodníci využívat sociální média v prodeji. Na základě systematické rešerše literatury, autor zjistil, že akademici, zkoumající danou problematiku, navrhují další výzkum, a to: v kterých konkrétních krocích se dají využít sociální média v prodeji (Salo, 2017). Autor se na základě toho rozhodl zjistit, jaké sociální sítě, různé technologie a pluginy se dají využít v B2B prodeji - tzv. social sellingu. Social selling se v této práci týká primárně procesu akvizice a okrajově péčí o stávající zákazníky. Autor si vybral kvalitativní průzkum pomocí 10 hloubkových polo-strukturovaných rozhovorů, aby odhalil jak, která sociální média to jsou, tak i motivaci prodejců, proč tato média používat/nepoužívat. Aby autor dodržel správnost vyhodnocení výsledků, data byla analyzována pomocí Tématické analýzy, která v této studii vykrystalizovala 2 hlavní strategické přístupy v social sellingu. Tyto přístupy (tzv. Push a Pull strategie) obsahují praktické příklady a konkrétní aktivity, které mohou prodejci využívat v každodenní praxi. Tyto výsledky jsou prezentovány s důrazem na praktičnost a jednoduchost implementace. Tvoří proto hlavní přínos autorovo výzkumu. V poslední části autor zmiňuje výzvy a manažerská doporučení, které mohou obchodníci využít v každodenním pracovním životě.This diploma thesis focuses on social media usage in B2B sales. Based on the systematic literature review conducted by the author, he has found out that recent researchers (Salo, 2017) suggest further research in the area of how and in which sales phase should various social networking sites, technologies and plugins used. To further fill this research gap, author decided to identify these social media and their usage among B2B salespeople in the so-called social selling process. The social selling process in this thesis applies mainly to acquiring new prospects and tangentially to taking care of existing clients (follow-up step). Author has chosen a qualitative research method via conducting 10 in-depth semi-structured interviews to reveal these instruments as well as motivation of a sales person on why to use social media in the selling process. The collected data was analyzed using Thematic analysis to ensure the right procedure and to identify main themes which crystalized into 2 main strategic approaches in social selling. These approaches (Push and Pull) include practical examples of concrete activities which sales people can use in their daily jobs and are presented with focus on practicality and ease of implementation. These also form the main contribution of author`s research. In the last part, author mentions challenges in social selling and recommended managerial implications for salesforce

    TeX v jednoduchém unixovém prostředí

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    summary:Při ladění TeXového dokumentu potřebujeme mnohokrát opakovaně pouštět TeX, podívat se, jak dopadl výsledek v prohlížeči DVI nebo PDF souboru, mrknout na výpis TeXu na terminálu, podívat se případně do logu a celou činnost opakovat. V tomto článku je ukázáno, jak tuto práci dělá autor článku. Proces "editor-TeX-kuk" je zde podporován jednoduchými unixovými nástroji: bashovým skriptem texloop, který si autor pro tyto účely vytvořil, dále terminálem Xterm a jednoduchým editorem, který umí navázat na klávesovou zkratku spuštění příkazu v systému. Čtenář se zde může inspirovat a přizpůsobit tyto nástroje svým vlastním potřebám. V článku je popsána funkce skriptu texloop, dále je neformálně rozveden dlouholetý vývoj autorova vztahu k textovým editorům a konečně je zde uvedena konfigurace terminálu Xterm, aby vyhovoval českému prostředí jak v kódování ISO-8859-2, tak v kódování UTF-8. Pro kódování UTF-8 si v závěru článku vygenerujeme TeXový formát csplain.summary:By debugging a TeX document it is necessary many times repeatedly to run TeX, to look for the result in DVI or PDF file, to gander the TeX output on the terminal, or eventually to have a look in the log-file, and all that action to repeat. In the paper it is show, how this work is made by author. The process '‘'editor-TeX-look' is supported by simple Unix tools: bash script texloop, created by author for these purposes, Xterm terminal and a simple editor, which is able to link to the shortcut key the activation of a system command. The reader could be inspired with the solution and to adapt these tools to his/her own needs. In the paper the function of the texloop script is described, and further the longstanding evolution of the author's relation to text editors is informal elaborated and finally a configuration of Xterm terminal, suitable for the czech environment with both ISO-8859-2 and UTF-8 encoding is introduced. For UTF-8 encoding the TeX format csplain is generated at the end of the paper

    Analýza perspektivy vedoucích prodeje na řízení pojišťovacích agentů v etnicky různorodých zastoupeních v Organizaci G, Malajsie.

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    Cílem této práce je odhalit klíčové faktory a výzvy spojené s řízením etnicky různorodého pojišťovacího zastoupení v oboru životního pojištění v Malajsii. Autor si klade za cíl zkoumat pohled vedoucích prodeje v Organizaci G v Malajsii na jejich způsob řízení agentů. Kombinované kvantitativní a kvalitativní metody budou použity prostřednictvím průzkumu a rozhovorů se 79 agenty a 12 vedoucími prodeje. Odpovědi budou analyzovány za účelem porozumění výzvám, kterým čelí vedoucí prodeje při řízení etnicky různorodého zastoupení, a zkoumat potenciální řešení. Autor navrhuje iniciativy a metody k posílení stylů vedení a zlepšení procesů pro udržení úspěšného zastoupení v kontextu etnické rozmanitosti.The goal of this thesis is to uncover the key factors and challenges in managing an ethnically diverse insurance agency in Malaysia's life insurance industry. The author aims to examine the sales managers' perspective in Organisation G, Malaysia, regarding their expression of managing their agents. Quantitative and qualitative methods will be employed through surveys and interviews among 79 agents and 12 sales managers. The responses will be analysed to understand the challenges sales managers face in managing a multi-ethnic agency and explore potential solutions. The author proposes initiatives and methods to enhance leadership styles and improve the processes for maintaining a successful agency in the context of multi-ethnicity

    AUTHOR BOOK

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    Vytvořil jsem autorskou knihu o čtyřiceti stránkách s ilustracemi a minimem textu. Kniha je černobílá, dominuje v ní tušová kresba štětcem a perem. Kromě té je v knize ale i text, který slouží jako poetické doplnění ilustrací. Obsah knihy se zaměřuje na úzký kruh přátel a zároveň vypovídá o autorovi jak vybranými motivy, situacemi tak linkou. Vyznění knihy je spíše pocitové, má zanechat dojem, ne popisně vysvětlovat.ObhájenoI have created author book that has 40 pages with ilustrations and minimum of text. The book is black and white and contains ink drawings. There is also text poetically coresponding with pictures
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