The Inhibition of Splicing of Glucose-6-phosphate Dehydrogenase mRNA During Starvation by Heterogeneous Nuclear Ribonucleoprotein K

Splicing of nascent RNA transcripts is an essential step in gene expression and a target of nutrient regulation. Glucose-6-phosphate dehydrogenase (G6PD) is a lipogenic gene whose expression is regulated exclusively at this posttranscriptional stage. Expression of G6PD mRNA increases 15- to 17-fold during refeeding and is inhibited 80-90% by starvation and the addition of polyunsaturated fat to the diet. The large changes in the accumulation of G6PD mRNA are due to changes the rate of pre-mRNA splicing and not changes in its transcription. In this regard, dietary carbohydrate enhances intron removal, which increases the accumulation of G6PD mRNA. Starvation alters pre-mRNA splicing by decreasing the rate of intron removal, leading to intron retention and a decrease in the accumulation of mature mRNA. A regulatory element within exon 12 of the G6PD pre-mRNA that contains both an ESS and an ESE mediates these changes in splicing efficiency. SR proteins, like SRp20, along with hnRNP K, L and A2/B1 bind to this regulatory region. Starvation caused an increase in the expression of heterogeneous nuclear ribonucleoprotein (hnRNP) K protein and this increase coincided with the increase in the binding of hnRNP K to the regulatory element and a decrease in the expression of G6PD mRNA in vivo. HnRNP K bound to two C-rich motifs forming an ESS within exon 12. Overexpression of hnRNP K decreased the splicing and expression of G6PD mRNA, while siRNA-mediated depletion of hnRNP K caused an increase in the splicing and expression of G6PD mRNA. HnRNP K binding to the C- rich motifs blocked binding of serine-arginine rich, splicing factor 3 (SRSF3), a splicing enhancer. Thus hnRNP K is a nutrient regulated splicing factor responsible for the inhibition of the splicing of G6PD during starvation

A Human Being Wrote This Law Review Article: GPT-3 and the Practice of Law

Artificial intelligence tools can now “write” in such a sophisticated manner that they fool people into believing that a human wrote the text. None are better at writing than GPT-3, released in 2020 for beta testing and coming to commercial markets in 2021. GPT-3 was trained on a massive dataset that included scrapes of language from sources ranging from the NYTimes to Reddit boards. And so, it comes as no surprise that researchers have already documented incidences of bias where GPT-3 spews toxic language. But because GPT-3 is so good at “writing,” and can be easily trained to write in a specific voice — from classic Shakespeare to Taylor Swift — it is poised for wide adoption in the field of law. This Article explores the ethical considerations that will follow from GPT-3’s introduction into lawyers’ practices. GPT-3 is new, but the use of AI in the field of law is not. AI has already thoroughly suffused the practice of law. GPT-3 is likely to take hold as well, generating some early excitement that it and other AI tools could help close the access to justice gap. That excitement should nevertheless be tempered with a realistic assessment of GPT-3’s tendency to produce biased outputs. As amended, the Model Rules of Professional Conduct acknowledge the impact of technology on the profession and provide some guard rails for its use by lawyers. This Article is the first to apply the current guidance to GPT-3, concluding that it is inadequate. I examine three specific Model Rules — Rule 1.1 (Competence), Rule 5.3 (Supervision of Nonlawyer Assistance), and Rule 8.4(g) (Bias) — and propose amendments that focus lawyers on their duties and require them to regularly educate themselves about pros and cons of using AI to ensure the ethical use of this emerging technology

The Most Common Vocal Fault in the Baritone Voice

The purpose of this research project is to create an approachable guide to avoiding the most common vocal fault found in the baritone singing voice. The specific fault being discussed has been coined the “baritone swallow.” This document will explore the history of the baritone singing voice along with information regarding vocal fach identification, an in-depth study of this common vocal fault frequently experienced by baritone singers, and a fault-specific guide to identifying and addressing the “baritone swallow.

Guides to administrator behavior

Rules of thumb for everyday life as an administrator

Blockchain Safe Harbor? Applying the Lessons Learned From Early Internet Regulation

It has been more than a quarter century since Congress enacted twin safe harbor provisions to help protect and encourage the growth of a nascent internet by removing some liability and regulatory uncertainty. Today, there are calls for a similar safe harbor provision for blockchain, the technology behind cryptocurrencies and smart contracts. What lessons have we learned from the implementation of the internet safe harbor provisions, Section 230 of the Communications Decency Act, and Section 512 of the Digital Millennium Copyright Act? This Article charts the history of those provisions and their judicial construction over the decades. It also examines the criticism of these safe harbors, including that they have done too much to immunize large technology companies from the harm caused by their products. Blockchain technology shares a common history with the internet, and blockchain today is in a similar position to internet in the mid 1990s. Through cataloguing the lessons of internet regulation, this Article provides important considerations for regulators to bear in mind as they consider implementing safe harbor provisions for blockchain applications

Solvable Polynomial Ideals: The Ideal Reflection for Program Analysis

This paper presents a program analysis method that generates program summaries involving polynomial arithmetic. Our approach builds on prior techniques that use solvable polynomial maps for summarizing loops. These techniques are able to generate all polynomial invariants for a restricted class of programs, but cannot be applied to programs outside of this class -- for instance, programs with nested loops, conditional branching, unstructured control flow, etc. There currently lacks approaches to apply these prior methods to the case of general programs. This paper bridges that gap. Instead of restricting the kinds of programs we can handle, our method abstracts every loop into a model that can be solved with prior techniques, bringing to bear prior work on solvable polynomial maps to general programs. While no method can generate all polynomial invariants for arbitrary programs, our method establishes its merit through a monotonicty result. We have implemented our techniques, and tested them on a suite of benchmarks from the literature. Our experiments indicate our techniques show promise on challenging verification tasks requiring non-linear reasoning.Comment: Long version of an article to appear at the 51st ACM SIGPLAN Symposium on Principles of Programming Languages (POPL 2024). This version is a replacement of an earlier long version where typos have been fixed, DOI's have been added to references when able, and a data availability statement has been adde

Launching the Project: An Exercise for Demonstrating the Impact of Team Communications on Project Success

Research amply demonstrates that communication is an important determinate of project team success. Teaching team communication skills can be difficult, however, as team assignments are typically completed outside the classroom. Team communication education generally focuses on team dynamics or the interpersonal communication among team members, leaving aside some of the most important elements of project management communication in the development of information systems: task definition and assignment, project documentation, and integration of new members into the ongoing communication process. A self-contained learning unit was designed to introduce a class of senior-level information systems students to these group communication issues and show their importance to the successful completion of a project

“A Change is Gonna Come:” Developing a Liability Framework for Social Media Algorithmic Amplification

From the moment social media companies like Facebook were created, they have been largely immune to suit for the actions they take with respect to user content. This is thanks to Section 230 of the Communications Decency Act, 47 U.S.C. § 230, which offers broad immunity to sites for content posted by users. But seemingly the only thing a deeply divided legislature can agree on is that Section 230 must be amended, and soon. Once that immunity is altered, either by Congress or the courts, these companies may be liable for the decisions and actions of their algorithmic recommendation systems, artificial intelligence models that sometimes amplify the worst in our society, as Facebook whistleblower Frances Haugen explained to Congress in her testimony. But what, exactly, will it look like to sue a company for the actions of an algorithm? Whether through torts like defamation or under certain statutes, such as those aimed at curbing terrorism, the mechanics of bringing such a claim will surely occupy academics and practitioners in the wake of changes to Section 230. To that end, this Article is the first to examine how the issue of algorithmic amplification might be addressed by agency principles of direct and vicarious liability, specifically within the context of holding social media companies accountable. As such, this Article covers the basics of algorithmic recommendation systems, discussing them in layman’s terms and explaining why Section 230 reform may spur claims that have a profound impact on traditional tort law. The Article looks to sex trafficking claims made against social media companies—an area already exempted from Section 230’s shield—as an early model of how courts might address other claims against these companies. It also examines the potential hurdles, such as causation, that will remain even when Section 230 is amended. It concludes by offering certain policy considerations for both lawmakers and jurists