Focused CRISPR‑Cas9 genetic screening reveals USO1 as a vulnerability in B‑cell acute lymphoblastic leukemia

Abstract Post-transcriptional gene regulation, including that by RNA binding proteins (RBPs), has recently been described as an important mechanism in cancer. We had previously identified a set of RBPs that were highly dysregulated in B-cell acute lymphoblastic leukemia (B-ALL) with MLL translocations, which carry a poor prognosis. Here, we sought to functionally characterize these dysregulated RBP genes by performing a focused CRISPR dropout screen in B-ALL cell lines, finding dependencies on several genes including EIF3E, EPRS and USO1. Validating our findings, CRISPR/Cas9-mediated disruption of USO1 in MLL-translocated B-ALL cells reduced cell growth, promoted cell death, and altered the cell cycle. Transcriptomic analysis of USO1-deficient cells revealed alterations in pathways related to mTOR signaling, RNA metabolism, and targets of MYC. In addition, USO1-regulated genes from these experimental samples were significantly and concordantly correlated with USO1 expression in primary samples collected from B-ALL patients. Lastly, we found that loss of Uso1 inhibited colony formation of MLL-transformed in primary bone marrow cells from Cas9-EGFP mice. Together, our findings demonstrate an approach to performing focused sub-genomic CRISPR screens and highlight a putative RBP vulnerability in MLL-translocated B-ALL, thus identifying potential therapeutic targets in this disease

Bright Patterns as an Ethical Approach to Counteract Dark Patterns : A Closer Investigation of The Ethics of Persuasive Design

The purpose of this study is to explore the ethical dilemma in design that User Experience (UX) designers encounter in their workplace, consumers’ perception of ethics in bright patterns and dark patterns, and consumers’ decisions between bright patterns and dark patterns. The former aims to understand the reason behind the prevalence of dark patterns, while the latter aims to determine whether bright patterns are a potential ethical approach that designers can adopt in the future. In this study, the methods semi-structured interview and within-subjects experiment with follow-up interview were conducted to gather empirical data. For both methods, a content analysis was selected to analyze the empirical data, which resulted in findings that answered the research questions of this study. The findings show that (1) authority to decide how designers should address ethics in design is more distributed to those investing in a product development project, (2) most ethical issues revolve around challenges of working in an ethical manner rather than bad practices of incorporating ethics in design work, (3) designers adopt one or more ethical approaches to stay ethical and /or address ethical issues that arise in their workplace, (4) some specific bright patterns and dark patterns have no influence on consumer decisions while other specific bright patterns and dark patterns influence consumer decisions, and (5) consumers perceive bright patterns to be more ethical than dark patterns in terms of freedom of choice and transparency.

Bright Patterns as an Ethical Approach to Counteract Dark Patterns : A Closer Investigation of The Ethics of Persuasive Design

The purpose of this study is to explore the ethical dilemma in design that User Experience (UX) designers encounter in their workplace, consumers’ perception of ethics in bright patterns and dark patterns, and consumers’ decisions between bright patterns and dark patterns. The former aims to understand the reason behind the prevalence of dark patterns, while the latter aims to determine whether bright patterns are a potential ethical approach that designers can adopt in the future. In this study, the methods semi-structured interview and within-subjects experiment with follow-up interview were conducted to gather empirical data. For both methods, a content analysis was selected to analyze the empirical data, which resulted in findings that answered the research questions of this study. The findings show that (1) authority to decide how designers should address ethics in design is more distributed to those investing in a product development project, (2) most ethical issues revolve around challenges of working in an ethical manner rather than bad practices of incorporating ethics in design work, (3) designers adopt one or more ethical approaches to stay ethical and /or address ethical issues that arise in their workplace, (4) some specific bright patterns and dark patterns have no influence on consumer decisions while other specific bright patterns and dark patterns influence consumer decisions, and (5) consumers perceive bright patterns to be more ethical than dark patterns in terms of freedom of choice and transparency.

A study of user experience (UX) in the context of cross-channel : The users’ experience of book loan at the library of University of Borås

The bachelor thesis aims to explore whether students perceive the usage of self-service technology (SST) as positive, neutral or negative, which occurs before, under and after a visit at the library of University of Borås. In this paper, a qualitative user diary was used as a method to gather empirical data. An established UX method, customer journey mapping (CJM), was selected to analyze the empirical findings. The findings were further analyzed with a theoretical framework of the predecessor David Benyon to gain a deeper understanding of user experience in a cross-channel context. The study shows that students are overall positive to the usage of SST, but a deficiency of information affects the positive experience throughout the library

Focused CRISPR-Cas9 genetic screening reveals USO1 as a vulnerability in B-cell acute lymphoblastic leukemia.

Post-transcriptional gene regulation, including that by RNA binding proteins (RBPs), has recently been described as an important mechanism in cancer. We had previously identified a set of RBPs that were highly dysregulated in B-cell acute lymphoblastic leukemia (B-ALL) with MLL translocations, which carry a poor prognosis. Here, we sought to functionally characterize these dysregulated RBP genes by performing a focused CRISPR dropout screen in B-ALL cell lines, finding dependencies on several genes including EIF3E, EPRS and USO1. Validating our findings, CRISPR/Cas9-mediated disruption of USO1 in MLL-translocated B-ALL cells reduced cell growth, promoted cell death, and altered the cell cycle. Transcriptomic analysis of USO1-deficient cells revealed alterations in pathways related to mTOR signaling, RNA metabolism, and targets of MYC. In addition, USO1-regulated genes from these experimental samples were significantly and concordantly correlated with USO1 expression in primary samples collected from B-ALL patients. Lastly, we found that loss of Uso1 inhibited colony formation of MLL-transformed in primary bone marrow cells from Cas9-EGFP mice. Together, our findings demonstrate an approach to performing focused sub-genomic CRISPR screens and highlight a putative RBP vulnerability in MLL-translocated B-ALL, thus identifying potential therapeutic targets in this disease