Section 2-318 of the UCC: The Sleeping Giant

The acceptance, application, and development of Section 2-318 of the Uniform Commercial Codemhas caused more trouble and confusion than the appearance of Darwin\u27s theory of evolution in Tennessee. Overlooking the obvious possible solution of amending Section 2-318, most states have retained a written but unexercised statute and thereby compelled courts to stretch, bend and squeeze breach of warranty into the realm of strict liability in tort

Artificial Intelligence in Gastrointestinal Endoscopy.

Artificial intelligence (AI) is rapidly integrating into modern technology and clinical practice. Although in its nascency, AI has become a hot topic of investigation for applications in clinical practice. Multiple fields of medicine have embraced the possibility of a future with AI assisting in diagnosis and pathology applications. In the field of gastroenterology, AI has been studied as a tool to assist in risk stratification, diagnosis, and pathologic identification. Specifically, AI has become of great interest in endoscopy as a technology with substantial potential to revolutionize the practice of a modern gastroenterologist. From cancer screening to automated report generation, AI has touched upon all aspects of modern endoscopy. Here, we review landmark AI developments in endoscopy. Starting with broad definitions to develop understanding, we will summarize the current state of AI research and its potential applications. With innovation developing rapidly, this article touches upon the remarkable advances in AI-assisted endoscopy since its initial evaluation at the turn of the millennium, and the potential impact these AI models may have on the modern clinical practice. As with any discussion of new technology, its limitations must also be understood to apply clinical AI tools successfully

The Ford Nuclear Reactor Control System

Submitted for presentation at the Fall Meeting of the American Nuclear Society held in New York on October 28, 1957.http://deepblue.lib.umich.edu/bitstream/2027.42/86114/1/MMPP FNR Control 28 Oct 1957 ANS.PDF-

Genomic and clinical characterization of stromal infiltration markers in prostate cancer

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154519/1/cncr32688_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154519/2/cncr32688.pd

Role of genetic testing for inherited prostate cancer risk: Philadelphia prostate cancer consensus conference 2017

Purpose: Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-dri

Dual inhibition of AKT‐mTOR and AR signaling by targeting HDAC3 in PTEN‐ or SPOP‐mutated prostate cancer

Abstract AKT‐mTOR and androgen receptor (AR) signaling pathways are aberrantly activated in prostate cancer due to frequent PTEN deletions or SPOP mutations. A clinical barrier is that targeting one of them often activates the other. Here, we demonstrate that HDAC3 augments AKT phosphorylation in prostate cancer cells and its overexpression correlates with AKT phosphorylation in patient samples. HDAC3 facilitates lysine‐63‐chain polyubiquitination and phosphorylation of AKT, and this effect is mediated by AKT deacetylation at lysine 14 and 20 residues and HDAC3 interaction with the scaffold protein APPL1. Conditional homozygous deletion of Hdac3 suppresses prostate tumorigenesis and progression by concomitant blockade of AKT and AR signaling in the Pten knockout mouse model. Pharmacological inhibition of HDAC3 using a selective HDAC3 inhibitor RGFP966 inhibits growth of both PTEN‐deficient and SPOP‐mutated prostate cancer cells in culture, patient‐derived organoids and xenografts in mice. Our study identifies HDAC3 as a common upstream activator of AKT and AR signaling and reveals that dual inhibition of AKT and AR pathways is achievable by single‐agent targeting of HDAC3 in prostate cancer

Master Transcription Factor Reprogramming Unleashes Selective Translation Promoting Castration Resistance and Immune Evasion in Lethal Prostate Cancer

Signaling rewiring allows tumors to survive therapy. Here we show that the decrease of the master regulator microphthalmia transcription factor (MITF) in lethal prostate cancer unleashes eukaryotic initiation factor 3B (eIF3B)-dependent translation reprogramming of key mRNAs conferring resistance to androgen deprivation therapy (ADT) and promoting immune evasion. Mechanistically, MITF represses through direct promoter binding eIF3B, which in turn regulates the translation of specific mRNAs. Genome-wide eIF3B enhanced cross-linking immunoprecipitation sequencing (eCLIP-seq) showed specialized binding to a UC-rich motif present in subsets of 5\u27 untranslated regions. Indeed, translation of the androgen receptor and major histocompatibility complex I (MHC-I) through this motif is sensitive to eIF3B amount. Notably, pharmacologic targeting of eIF3B-dependent translation in preclinical models sensitizes prostate cancer to ADT and anti-PD-1 therapy. These findings uncover a hidden connection between transcriptional and translational rewiring promoting therapy-refractory lethal prostate cancer and provide a druggable mechanism that may transcend into effective combined therapeutic strategies. SIGNIFICANCE: Our study shows that specialized eIF3B-dependent translation of specific mRNAs released upon downregulation of the master transcription factor MITF confers castration resistance and immune evasion in lethal prostate cancer. Pharmacologic targeting of this mechanism delays castration resistance and increases immune-checkpoint efficacy. This article is featured in Selected Articles from This Issue, p. 2489

Section 2-318 of the UCC: The Sleeping Giant

The acceptance, application, and development of Section 2-318 of the Uniform Commercial Codemhas caused more trouble and confusion than the appearance of Darwin\u27s theory of evolution in Tennessee. Overlooking the obvious possible solution of amending Section 2-318, most states have retained a written but unexercised statute and thereby compelled courts to stretch, bend and squeeze breach of warranty into the realm of strict liability in tort