65 research outputs found
PREDICTIVE CHEMINFORMATICS ANALYSIS OF DIVERSE CHEMOGENOMICS DATA SOURCES: APPLICATIONS TO DRUG DISCOVERY, ASSAY INTERFERENCE, AND TEXT MINING
Get PDFIn this dissertation, we describe the cheminformatics analysis of diverse chemogenomics data sources as well as the application of these data to several drug discovery efforts. In Chapter 1, we describe the discovery and characterization of novel Ebola virus inhibitors through QSAR-based virtual screening. In Chapter 2, we report the discovery and analysis of a series of potent and selective doublecortin-like kinase 1 (DCLK1) inhibitors using QSAR modeling, virtual screening, Matched Molecular Pair Analysis (MMPA), and molecular docking. In Chapter 3, we performed a large-scale analysis of publicly available data in PubChem to probe the reliability and applicability of Pan-Assay INterference compoundS (PAINS) alerts, a popular computational drug screening tool. In Chapter 4, we explore the PubMed database as a novel source of biomedical data and describe the development of Chemotext, a publicly available web server capable of text-mining the published literature.Doctor of Philosoph
Jennifer Stephen, tuba; Leslee Heys, piano
No full textThe program was printed without a date; this is an estimated date
Cory W. Thorne, trombone; Sally Rowsell, piano; Stephen Candow, organ
No full textPresented in partial fulfilment of the requirements for Music 450B
Data and codes behind "Crowdsourced mapping of unexplored target space of kinase inhibitors"
No full textThis repository contains the data underlying the figures in the journal publication describing the IDG-DREAM Drug Kinase Binding Prediction Challenge [1] as well as archives of the two following GitHub repositories:
IDG-DREAM-Challenge-Analysis-ncomms.zip (https://github.com/Sage-Bionetworks/IDG-DREAM-Challenge-Analysis): codes for reproducing the analyses described in [1]; licence Apache 2.0.
IDG-DREAM-Drug-Kinase-Challenge-ncomms.zip (https://github.com/Sage-Bionetworks/IDG-DREAM-Drug-Kinase-Challenge): codes used for the Challenge scoring; licence Apache 2.0.
References
[1] Cichońska A, Ravikumar B, Allaway RJ, Wan F, Park S, Isayev O, Li S, Mason M, Lamb A, Tanoli Z, Jeon M, Kim S, Popova M, Capuzzi S, Zeng J, Dang K, Koytiger G, Kang J, Wells CI, Willson TM, The IDG-DREAM Drug-Kinase Binding Prediction Challenge Consortium, Oprea TI, Schlessinger A, Drewry DH, Stolovitzky G, Wennerberg K, Guinney J, Aittokallio T. Crowdsourced mapping of unexplored target space of kinase inhibitors. Nature Communications 2021
Introduction to the Counseling Profession
No full textIntroduction to the Counseling Profession is a comprehensive overview of the history and foundational concepts of counseling, offering the most current and relevant breadth of coverage available. Students will gain insight into the myriad issues that surround not only the process of counseling and its many populations but also the personal dynamics that have an impact on this process. The contributed-author format provides state-of-the-art information from experts in their respective fields while maintaining a consistent structure and message.
This edition has been brought in line with the 2009 Council for the Accreditation of Counseling and Related Educational Programs (CACREP) standards and includes chapters on each of the CACREP specializations. Topics rarely treated in other introductory texts are addressed, such as research and writing in counseling, technology and counseling, and self-care and growth
Phantom PAINS: Problems with the Utility of Alerts for Pan‑Assay INterference CompoundS
Get PDFThe
use of substructural alerts to identify Pan-Assay INterference compoundS (PAINS)
has become a common component of the triage process in biological
screening campaigns. These alerts, however, were originally derived
from a proprietary library tested in just six assays measuring protein–protein
interaction (PPI) inhibition using the AlphaScreen detection technology
only; moreover, 68% (328 out of the 480 alerts) were derived from
four or fewer compounds. In an effort to assess the reliability of
these alerts as indicators of pan-assay interference, we performed
a large-scale analysis of the impact of PAINS alerts on compound promiscuity
in bioassays using publicly available data in PubChem. We found that
the majority (97%) of all compounds containing PAINS alerts were actually
infrequent hitters in AlphaScreen assays measuring PPI inhibition.
We also found that the presence of PAINS alerts, contrary to expectations,
did not reflect any heightened assay activity trends across all assays
in PubChem including AlphaScreen, luciferase, beta-lactamase, or fluorescence-based
assays. In addition, 109 PAINS alerts were present in 3570 extensively
assayed, but consistently inactive compounds called Dark Chemical
Matter. Finally, we observed that 87 small molecule FDA-approved drugs
contained PAINS alerts and profiled their bioassay activity. Based
on this detailed analysis of PAINS alerts in nonproprietary compound
libraries, we caution against the blind use of PAINS filters to detect
and triage compounds with possible PAINS liabilities and recommend
that such conclusions should be drawn only by conducting orthogonal
experiments
Effect of Xuezhikang, an extract from red yeast Chinese rice, on coronary events in a Chinese population with previous myocardial infarction
No full textResults of well-controlled prospective clinical trials showed the efficacy of lipid-lowering therapies in the reduction of cardiovascular (CV) events in western populations, but they were not reported with a Chinese population. This multicenter study was conducted to determine the effects of Xuezhikang (XZK), a partially purified extract of red yeast rice, on lipoprotein and CV end points in Chinese patients who experienced a previous myocardial infarction. Nearly 5,000 of these patients with average low-density lipoprotein cholesterol levels at baseline were randomly assigned either to placebo or to XZK daily for an average of 4.5 years. The primary end point was a major coronary event that included nonfatal myocardial infarction and death from coronary heart disease. Frequencies of the primary end point were 10.4% in the placebo group and 5.7% in the XZK-treated group, with absolute and relative decreases of 4.7% and 45%, respectively. Treatment with XZK also significantly decreased CV and total mortality by 30% and 33%, the need for coronary revascularization by 1/3, and lowered total and low-density lipoprotein cholesterol and triglycerides, but raised high-density lipoprotein cholesterol levels. In conclusion, long-term therapy with XZK significantly decreased the recurrence of coronary events and the occurrence of new CV events and deaths, improved lipoprotein regulation, and was safe and well tolerated
A Pedagogical Approach to the Teaching of Six Selected Formative Euphonium Recital Pieces: Annotations, Exercises and Recording
Get PDFabstract: The purpose of this project was to provide a pedagogical resource for students and teachers to utilize when preparing six standard formative pieces from the euphonium repertoire. The guided practice sections are written in plain English with several instances of first person writing to explain certain concepts in a less formal way. This was done so that any teacher, regardless of level could help a younger, more inexperienced student. In addition, the sections of guided practice were written to help those teachers who may or may not be intimately familiar with the works chosen. The recording was designed to present the music in current published format, with no improvisation by the soloist. The solos that were chosen are either college preparatory pieces, or formative works for the younger collegiate musician. All of the pieces included are published, and as of September 2010, available for purchase. The works included are: Six Studies in English Folk Song, by Ralph Vaughan Williams, ed. Paul Droste, Introduction and Dance, by J. Edouard Barat, ed. Glenn Smith, Andante et Allegro, by Joseph- Guy Ropartz, ed. Shapiro, Sonata for Unaccompanied Euphonium (or Trombone), by Fred L. Clinard, Jr., Suite for Baritone, by Don Haddad, and Andante and Rondo, by Antonio Capuzzi, ed. Philip Catelinet.Dissertation/ThesisD.M.A. Music 201
Phantom PAINS: Problems with the Utility of Alerts for <u>P</u>an-<u>A</u>ssay <u>IN</u>terference Compound<u>S</u>
No full textQSAR modeling of Tox21 challenge stress response and nuclear receptor signaling toxicity assays
Get PDFThe ability to determine which environmental chemicals pose the greatest potential threats to human health remains one of the major concerns in regulatory toxicology. Computation methods that can accurately predict the chemicals’ toxic potential in silico are increasingly sought-after to replace in vitro high-throughput screening (HTS) as well as controversial and costly in vivo animal studies. To this end, we have built Quantitative Structure-Activity Relationship (QSAR) models of twelve (12) stress response and nuclear receptor signaling pathways toxicity assays as part of the 2014 Tox21 Challenge. Our models were built using the Random Forest, Deep Neural Networks and various combinations of descriptors and balancing protocols. All of our models were statistically significant for each of the 12 assays with the balanced accuracy in the range between 0.58 and 0.82. Our results also show that models built with Deep Neural Networks had high accuracy than those developed with simple machine learning algorithms and that dataset balancing led to a significant accuracy decrease
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