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"Lewis, Brian"
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Humpty Dumpty and Humpty Dumpty at sea
Presents the traditional nursery rhyme, a line at a time then as a whole, followed by a new rhyme. Includes \"Notes for adults\" and reading tips.
Book
BRD4 is an atypical kinase that phosphorylates Serine2 of the RNA Polymerase II carboxy-terminal domain
The bromodomain protein, BRD4, has been identified recently as a therapeutic target in acute myeloid leukemia, multiple myeloma, Burkitt’s lymphoma, NUT midline carcinoma, colon cancer, and inflammatory disease; its loss is a prognostic signature for metastatic breast cancer. BRD4 also contributes to regulation of both cell cycle and transcription of oncogenes, HIV, and human papilloma virus (HPV). Despite its role in a broad range of biological processes, the precise molecular mechanism of BRD4 function remains unknown. We report that BRD4 is an atypical kinase that binds to the carboxyl-terminal domain (CTD) of RNA polymerase II and directly phosphorylates its serine 2 (Ser2) sites both in vitro and in vivo under conditions where other CTD kinases are inactive. Phosphorylation of the CTD Ser2 is inhibited in vivo by a BRD4 inhibitor that blocks its binding to chromatin. Our finding that BRD4 is an RNA polymerase II CTD Ser2 kinase implicates it as a regulator of eukaryotic transcription.
Journal Article
Krüppel-Like Factor 4, a Tumor Suppressor in Hepatocellular Carcinoma Cells Reverts Epithelial Mesenchymal Transition by Suppressing Slug Expression
Krüppel-like factor 4 (KLF4) is a zinc-finger transcription factor that plays an important role in differentiation and pathogenesis. KLF4 has been suggested to act as an oncogene or tumor suppressor in different tumor types. However, the role of KLF4 in hepatocellular carcinoma (HCC) remains unclear. Here, we demonstrate that forced expression of Klf4 in murine HCC cell lines reduced anchorage-independent growth in soft agar as well as cell migration and invasion activities in vitro. Ectopic Klf4 expression impaired subcutaneous tumor growth and lung colonization in vivo. By contrast, Klf4 knockdown enhanced HCC cell migration. Interestingly, ectopic expression of Klf4 changed the morphology of murine HCC cells to a more epithelial phenotype. Associated with this, we found that expression of Slug, a critical epithelial mesenchymal transition (EMT)-related transcription factor, was significantly down-regulated in Klf4-expressing cells. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays showed that Klf4 is able to bind and repress the activity of the Slug promoter. Furthermore, ectopic Slug expression partially reverts the Klf4-mediated phenotypes. Consistent with a role as a tumor suppressor in HCC, analysis of the public microarray databases from Oncomine revealed reduced KLF4 expression in human HCC tissues in comparison with normal liver tissues in 3 out of 4 data sets. By quantitative reverse transcription-polymerase chain reaction (qRT-PCR), we found reduced KLF4 mRNA in 50% of HCC tissues. Importantly, an inverse correlation between the expression of KLF4 and SLUG was found in HCC tissues. Our data suggest that KLF4 acts as a tumor suppressor in HCC cells, in part by suppressing SLUG transcription.
Journal Article
Aircraft control and simulation : dynamics, controls design, and autonomous systems
This third edition is a comprehensive guide to aircraft control and simulation. The updated text covers flight control systems, flight dynamics, aircraft modelling, and flight simulation from both classical design and modern perspectives, as well as two new chapters on the modelling, simulation, and adaptive control of unmanned aerial vehicles.
Book
The best American mystery stories 2016
The Best American Mystery Stories 2016 is a feast of both literary crime and hard-boiled detection, featuring a seemingly innocent murderer, a drug dealer in love, a drunken prank gone terribly wrong, and plenty of other surprising twists and turns.
Book
Design and validation of a semi-automatic bone segmentation algorithm from MRI to improve research efficiency
Segmentation of medical images into different tissue types is essential for many advancements in orthopaedic research; however, manual segmentation techniques can be time- and cost-prohibitive. The purpose of this work was to develop a semi-automatic segmentation algorithm that leverages gradients in spatial intensity to isolate the patella bone from magnetic resonance (MR) images of the knee that does not require a training set. The developed algorithm was validated in a sample of four human participants (in vivo) and three porcine stifle joints (ex vivo) using both magnetic resonance imaging (MRI) and computed tomography (CT). We assessed the repeatability (expressed as mean ± standard deviation) of the semi-automatic segmentation technique on: (1) the same MRI scan twice (Dice similarity coefficient = 0.988 ± 0.002; surface distance = − 0.01 ± 0.001 mm), (2) the scan/re-scan repeatability of the segmentation technique (surface distance = − 0.02 ± 0.03 mm), (3) how the semi-automatic segmentation technique compared to manual MRI segmentation (surface distance = − 0.02 ± 0.08 mm), and (4) how the semi-automatic segmentation technique compared when applied to both MRI and CT images of the same specimens (surface distance = − 0.02 ± 0.06 mm). Mean surface distances perpendicular to the cartilage surface were computed between pairs of patellar bone models. Critically, the semi-automatic segmentation algorithm developed in this work reduced segmentation time by approximately 75%. This method is promising for improving research throughput and potentially for use in generating training data for deep learning algorithms.
Journal Article
Low-Cost Spinning Disk Confocal Microscopy with a 25-Megapixel Camera
Spinning disk confocal microscopy enables fast optical sectioning with low phototoxicity but is often inaccessible due to high hardware costs. We present a lower-cost solution using a 25-megapixel machine vision CMOS camera and a custom-built spinning disk. This camera uses a back-illuminated sensor with high quantum efficiency and low read noise. High-resolution images of Thy1-GFP mouse brain slices, Drosophila embryos and larvae, and H&E-stained rat testis verified performance across 3D tissue volumes. The measured resolution was 215.8 nm in X, Y and 521.9 nm in Z with a 60×/1.42 NA objective. The custom disk, made with 18 µm pinholes (180 µm pitch) on a chrome photomask and mounted to an optical chopper motor, enables stable, near-telecentric imaging at lower magnifications. Micromanager software integration allows synchronized control of all hardware, which demonstrates that affordable CMOS sensors can potentially replace sCMOS in spinning disk microscopy, offering an open-access, scalable solution for advanced imaging.
Journal Article
Gastrointestinal decontamination: Recent utilization trends
Gastrointestinal (GI) decontamination was once a mainstay in the treatment of toxicologic ingestions but has become less common over the past 30 years. Fifteen percent of toxic exposures reported to the American Association of Poison Control Centers in 1985 received ipecac compared to 0.003% in 2018; in 1995, 7.7% received activated charcoal (AC) compared to 1.75% in 2018 [1]. Despite the decline in GI decontamination use, there may still be some indications for AC, whole bowel irrigation (WBI), and gastric lavage (GL) [2,3]. Although there has been a significant decline in the use of GI decontamination for toxicologic exposures, it is important to understand what methods are being employed and the types of exposures for which they are being utilized.This was a retrospective cohort study of patients from the Toxicology Investigators Consortium (ToxIC) Case Registry who had a toxicologic exposure and received a form of GI decontamination AC, WBI, or GL. The study includes all patients over a five year period (2014–2019) who met these criteria. Data collected included age, toxin and toxin class exposures, form of GI decontamination the patient received, and signs and symptoms exhibited by patients.
Journal Article