DOCSLIB.ORG

Global Analysis of Protein Folding Thermodynamics for Disease State Characterization

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Global Analysis of Protein Folding Thermodynamics for Disease State Characterization and Biomarker Discovery by Jagat Adhikari Department of Biochemistry Duke University Date:_______________________ Approved: ___________________________ Michael C. Fitzgerald, Supervisor ___________________________ Kenneth Kreuzer ___________________________ Terrence G. Oas ___________________________ Jiyong Hong ___________________________ Seok-Yong Lee Dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Biochemistry in the Graduate School of Duke University 2015 ABSTRACT Global Analysis of Protein Folding Thermodynamics for Disease State Characterization and Biomarker Discovery by Jagat Adhikari Department of Biochemistry Duke University Date:_______________________ Approved: ___________________________ Michael C. Fitzgerald, Supervisor ___________________________ Kenneth Kreuzer ___________________________ Terrence G. Oas ___________________________ Jiyong Hong ___________________________ Seok-Yong Lee An abstract of a dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Biochemistry in the Graduate School of Duke University 2015 Copyright by Jagat Adhikari 2015 Abstract Protein biomarkers can facilitate the diagnosis of many diseases such as cancer and they can be important for the development of effective therapeutic interventions. Current large-scale biomarker discovery and disease state characterization studies have largely focused on the global analysis of gene and protein expression levels, which are not directly tied to function. Moreover, functionally significant proteins with similar expression levels go undetected in the current paradigm of using gene and protein expression level analyses for protein biomarker discovery. Protein-ligand interactions play an important role in biological processes. A number of diseases such as cancer are reported to have altered protein interaction networks. Current understanding of biophysical properties and consequences of altered protein interaction network in disease state is limited due to the lack of reproducible and high-throughput methods to make such measurements. Thermodynamic stability measurements can report on a wide range of biologically significant phenomena (e.g., point mutations, post-translational modifications, and new or altered binding interactions with cellular ligands) associated with proteins in different disease states. Investigated here is the use of thermodynamic stability measurements to probe the altered interaction networks and functions of proteins in disease states. This thesis outlines the development and application of mass spectrometry based methods for making proteome-wide thermodynamic measurements iv of protein stability in multifactorial complex diseases such as cancer. Initial work involved the development of SILAC-SPROX and SILAC-PP approaches for thermodynamic stability measurements in proof-of-concept studies with two test ligands, CsA and a non-hydrolyzable adenosine triphosphate (ATP) analogue, adenylyl imidodiphosphate (AMP-PNP). In these proof-of-principle studies, known direct binding target of CsA, cyclophilin A, was successfully identified and quantified. Similarly a number of known and previously unknown ATP binding proteins were also detected and quantified using these SILAC-based energetics approaches. Subsequent studies in this thesis involved thermodynamic stability measurements of proteins in the breast cancer cell line models to differentiate disease states. Using the SILAC-SPROX, ~800 proteins were assayed for changes in their protein folding behavior in three different cell line models of breast cancer including the MCF- 10A, MCF-7, and MDA-MB-231 cell lines. Approximately, 10-12% of the assayed proteins in the comparative analyses performed here exhibited differential stability in cell lysates prepared from the different cell lines. Thermodynamic profiling differences of 28 proteins identified with SILAC-SPROX strategy in MCF-10A versus MCF-7 cell line comparison were also confirmed with SILAC-PP technique. The thermodynamic analyses performed here enabled the non-tumorigenic MCF-10A breast cell line to be differentiated from the MCF-7 and MDA-MB-231 breast cancer cell lines. Differentiation of the less invasive MCF-7 breast cancer cell line from the more highly invasive MDA- v MB-231 breast cancer cell line was also possible using thermodynamic stability measurements. The differentially stabilized protein hits in these studies encompassed those with a wide range of functions and protein expression levels, and they included a significant fraction (~45%) with similar expression levels in the cell line comparisons. These proteins created novel molecular signatures to differentiate the cancer cell lines studied here. Our results suggest that protein folding and stability measurements complement the current paradigm of expression level analyses for biomarker discovery and help elucidate the molecular basis of disease. vi Dedication This work is dedicated to my beloved parents who nurtured me to be who I am. vii Contents Abstract ......................................................................................................................................... iv List of Tables .............................................................................................................................. xiii List of Figures .............................................................................................................................. xv List of Abbreviations .................................................................................................................. xx Acknowledgements .................................................................................................................. xxii 1. Background and Significance .................................................................................................. 1 1.1 Global Disease Burden and Early Diagnosis ................................................................ 1 1.2 Biomarker Discovery and Disease Characterization Studies ..................................... 2 1.3 Current Strategies for Global Disease State Characterization .................................... 4 1.3.1 Gene Expression Profiling .......................................................................................... 4 1.3.2 Protein Expression Profiling ...................................................................................... 5 1.3.2.1 Protein Microarrays ............................................................................................. 6 1.3.2.2 Mass Spectrometry based Protein Expression Analysis ................................. 7 1.3.3 Metabolomics ............................................................................................................... 9 1.4 Strategies beyond Expression Levels for Biomarker Analysis ................................. 10 1.4.1 Protein Interactome ................................................................................................... 10 1.4.2 Activity Based Protein Profiling .............................................................................. 11 1.5 Motivation and Significance of the Present Study ..................................................... 12 1.5.1 Protein Folding Thermodynamics in Disease states ............................................ 12 1.5.2 Approaches for Protein Folding and Thermodynamics Measurements ........... 13 viii 1.5.3 Stability of Proteins from Rates of Oxidation (SPROX) ....................................... 17 1.5.3.1 SPROX with Colorectal Cancer Tissue Lysates ............................................. 19 1.5.4 Pulse Proteolysis ........................................................................................................ 21 1.6 SILAC-based Quantitation Strategy ............................................................................ 22 1.7 Cell Line Models of Breast Cancer ............................................................................... 24 2. Proteomic Characterization of Therapeutic Response in Patient-Derived Tumor Explants of Colorectal Cancer in Murine Models. ................................................................. 26 2.1 Introduction ..................................................................................................................... 26 2.2 Experimental Procedures .............................................................................................. 29 2.2.1 Comparative Analyses Schematic ........................................................................... 29 2.2.2 Tissue Lysate Preparation ........................................................................................ 30 2.2.3 iTRAQ-SPROX Protocol ........................................................................................... 32 2.2.4 Methionine-containing Peptide Enrichment ......................................................... 33 2.2.5 LC-MS/MS Analysis. ................................................................................................. 34 2.2.6 iTRAQ-SPROX Data Analysis ................................................................................. 35 2.3 Results and Discussion .................................................................................................. 38 2.3.1 General Strategy .......................................................................................................
Recommended publications
  • The Campus Sexual Assault (CSA) Study Author(S): Christopher P

    The Campus Sexual Assault (CSA) Study Author(S): Christopher P

    The author(s) shown below used Federal funds provided by the U.S. Department of Justice and prepared the following final report: Document Title: The Campus Sexual Assault (CSA) Study Author(s): Christopher P. Krebs, Ph.D. ; Christine H. Lindquist, Ph.D. ; Tara D. Warner, M.A. ; Bonnie S. Fisher, Ph.D. ; Sandra L. Martin, Ph.D. Document No.: 221153 Date Received: December 2007 Award Number: 2004-WG-BX-0010 This report has not been published by the U.S. Department of Justice. To provide better customer service, NCJRS has made this Federally- funded grant final report available electronically in addition to traditional paper copies. Opinions or points of view expressed are those of the author(s) and do not necessarily reflect the official position or policies of the U.S. Department of Justice. This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s) and do not necessarily reflect the official position or policies of the U.S. Department of Justice. October 2007 The Campus Sexual Assault (CSA) Study Final Report NIJ Grant No. 2004-WG-BX-0010 Performance Period: January 2005 through December 2007 Prepared for National Institute of Justice 810 Seventh Street, NW Washington, DC 20001 Prepared by Christopher P. Krebs, Ph.D. Christine H. Lindquist, Ph.D. Tara D. Warner, M.A. RTI International 3040 Cornwallis Road Research Triangle Park, NC 27709 Bonnie S. Fisher, Ph.D. University of Cincinnati Sandra L.
  • Epithelial Delamination Is Protective During Pharmaceutical-Induced Enteropathy

    Epithelial Delamination Is Protective During Pharmaceutical-Induced Enteropathy

    Epithelial delamination is protective during pharmaceutical-induced enteropathy Scott T. Espenschieda, Mark R. Cronana, Molly A. Mattya, Olaf Muellera, Matthew R. Redinbob,c,d, David M. Tobina,e,f, and John F. Rawlsa,e,1 aDepartment of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710; bDepartment of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; cDepartment of Biochemistry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599; dDepartment of Microbiology and Immunology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599; eDepartment of Medicine, Duke University School of Medicine, Durham, NC 27710; and fDepartment of Immunology, Duke University School of Medicine, Durham, NC 27710 Edited by Dennis L. Kasper, Harvard Medical School, Boston, MA, and approved July 15, 2019 (received for review February 12, 2019) Intestinal epithelial cell (IEC) shedding is a fundamental response to in mediating intestinal responses to injury remains poorly un- intestinal damage, yet underlying mechanisms and functions have derstood for most xenobiotics. been difficult to define. Here we model chronic intestinal damage in Gastrointestinal pathology is common in people using phar- zebrafish larvae using the nonsteroidal antiinflammatory drug maceuticals, including nonsteroidal antiinflammatory drugs (NSAID) Glafenine. Glafenine induced the unfolded protein response (NSAIDs) (11). While gastric ulceration has historically been a (UPR) and inflammatory pathways in IECs, leading to delamination. defining clinical presentation of NSAID-induced enteropathy, Glafenine-induced inflammation was augmented by microbial colo- small intestinal pathology has also been observed, although the nizationandassociatedwithchanges in intestinal and environmental incidence may be underreported due to diagnostic limitations microbiotas.
  • Supplementary Table S1. Prioritization of Candidate FPC Susceptibility Genes by Private Heterozygous Ptvs

    Supplementary Table S1. Prioritization of Candidate FPC Susceptibility Genes by Private Heterozygous Ptvs

    Supplementary Table S1. Prioritization of candidate FPC susceptibility genes by private heterozygous PTVs Number of private Number of private Number FPC patient heterozygous PTVs in heterozygous PTVs in tumors with somatic FPC susceptibility Hereditary cancer Hereditary Gene FPC kindred BCCS samples mutation DNA repair gene Cancer driver gene gene gene pancreatitis gene ATM 19 1 - Yes Yes Yes Yes - SSPO 12 8 1 - - - - - DNAH14 10 3 - - - - - - CD36 9 3 - - - - - - TET2 9 1 - - Yes - - - MUC16 8 14 - - - - - - DNHD1 7 4 1 - - - - - DNMT3A 7 1 - - Yes - - - PKHD1L1 7 9 - - - - - - DNAH3 6 5 - - - - - - MYH7B 6 1 - - - - - - PKD1L2 6 6 - - - - - - POLN 6 2 - Yes - - - - POLQ 6 7 - Yes - - - - RP1L1 6 6 - - - - - - TTN 6 5 4 - - - - - WDR87 6 7 - - - - - - ABCA13 5 3 1 - - - - - ASXL1 5 1 - - Yes - - - BBS10 5 0 - - - - - - BRCA2 5 6 1 Yes Yes Yes Yes - CENPJ 5 1 - - - - - - CEP290 5 5 - - - - - - CYP3A5 5 2 - - - - - - DNAH12 5 6 - - - - - - DNAH6 5 1 1 - - - - - EPPK1 5 4 - - - - - - ESYT3 5 1 - - - - - - FRAS1 5 4 - - - - - - HGC6.3 5 0 - - - - - - IGFN1 5 5 - - - - - - KCP 5 4 - - - - - - LRRC43 5 0 - - - - - - MCTP2 5 1 - - - - - - MPO 5 1 - - - - - - MUC4 5 5 - - - - - - OBSCN 5 8 2 - - - - - PALB2 5 0 - Yes - Yes Yes - SLCO1B3 5 2 - - - - - - SYT15 5 3 - - - - - - XIRP2 5 3 1 - - - - - ZNF266 5 2 - - - - - - ZNF530 5 1 - - - - - - ACACB 4 1 1 - - - - - ALS2CL 4 2 - - - - - - AMER3 4 0 2 - - - - - ANKRD35 4 4 - - - - - - ATP10B 4 1 - - - - - - ATP8B3 4 6 - - - - - - C10orf95 4 0 - - - - - - C2orf88 4 0 - - - - - - C5orf42 4 2 - - - -
  • Alite Calcium Sulfoaluminate Cement: Chemistry and Thermodynamics

    Alite Calcium Sulfoaluminate Cement: Chemistry and Thermodynamics

    This is a repository copy of Alite calcium sulfoaluminate cement: chemistry and thermodynamics. White Rose Research Online URL for this paper: http://eprints.whiterose.ac.uk/144183/ Version: Accepted Version Article: Hanein, T. orcid.org/0000-0002-3009-703X, Duvallet, T.Y., Jewell, R.B. et al. (5 more authors) (2019) Alite calcium sulfoaluminate cement: chemistry and thermodynamics. Advances in Cement Research, 31 (3). pp. 94-105. ISSN 0951-7197 https://doi.org/10.1680/jadcr.18.00118 © 2019 ICE Publishing. This is an author produced version of a paper subsequently published in Advances in Cement Research. Uploaded in accordance with the publisher's self-archiving policy. Reuse Items deposited in White Rose Research Online are protected by copyright, with all rights reserved unless indicated otherwise. They may be downloaded and/or printed for private study, or other acts as permitted by national copyright laws. The publisher or other rights holders may allow further reproduction and re-use of the full text version. This is indicated by the licence information on the White Rose Research Online record for the item. Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing [email protected] including the URL of the record and the reason for the withdrawal request. [email protected] https://eprints.whiterose.ac.uk/ Abstract: Calcium sulfoaluminate (C$A) cement is a binder of increasing interest to the cement industry and as such is undergoing rapid development. Current formulations do not contain alite; however, it can be shown that hybrid C$A-alite cements can combine the favourable characteristics of Portland cement with those of C$A cement while also having a lower carbon footprint than the current generation of Portland cement clinkers.
  • Evaluating Nonpoint Source Critical Source Area Contributions at the Watershed Scale

    Evaluating Nonpoint Source Critical Source Area Contributions at the Watershed Scale

    TECHNICAL REPORTS:TECHNICAL SURFACE REPORTS WATER QUALITY Evaluating Nonpoint Source Critical Source Area Contributions at the Watershed Scale Michael J. White* USDA-ARS Daniel E. Storm and Philip R. Busteed Oklahoma State University Scott H. Stoodley AMEC Earth & Environmental Shannon J. Phillips Oklahoma Conservation Commission Areas with disproportionately high pollutant losses (i.e., ater quality impairment due to sediment and nutrients is a critical source areas [CSAs]) have been widely recognized as serious problem in the USA. In 2002, 45% of streams and priority areas for the control of nonpoint-source pollution. Th e W identifi cation and evaluation of CSAs at the watershed scale rivers and 47% of lakes and reservoirs were listed as impaired and allows state and federal programs to implement soil and water unable to support their designated uses (USEPA, 2007). Agricultural conservation measures where they are needed most. Despite production is the leading source of impairment for streams and rivers many potential advantages, many state and federal conservation in the USA (USEPA, 2007). Conservation practices can signifi cantly programs do not actively target CSAs. Th ere is a lack of reduce nonpoint-source pollution, but to be eff ective, appropriate research identifying the total CSA pollutant contribution at the watershed scale, and there is no quantitative assessment practices must be located to prevent the mobilization of pollutants or of program eff ectiveness if CSAs are actively targeted. Th e intercept them en route to streams. Th e placement of these practices purpose of this research was to identify and quantify sediment within a watershed signifi cantly infl uences their overall eff ectiveness and total phosphorus loads originating from CSAs at the (Gitau et al., 2004).
  • Supplemental Materials Supplemental Table 1

    Supplemental Materials Supplemental Table 1

    Electronic Supplementary Material (ESI) for RSC Advances. This journal is © The Royal Society of Chemistry 2016 Supplemental Materials Supplemental Table 1. The differentially expressed proteins from rat pancreas identified by proteomics (SAP vs. SO) No. Protein name Gene name ratio P value 1 Metallothionein Mt1m 3.35 6.34E-07 2 Neutrophil antibiotic peptide NP-2 Defa 3.3 8.39E-07 3 Ilf2 protein Ilf2 3.18 1.75E-06 4 Numb isoform o/o rCG 3.12 2.73E-06 5 Lysozyme Lyz2 3.01 5.63E-06 6 Glucagon Gcg 2.89 1.17E-05 7 Serine protease HTRA1 Htra1 2.75 2.97E-05 8 Alpha 2 macroglobulin cardiac isoform (Fragment) 2.75 2.97E-05 9 Myosin IF (Predicted) Myo1f 2.65 5.53E-05 10 Neuroendocrine secretory protein 55 Gnas 2.61 7.60E-05 11 Matrix metallopeptidase 8 Mmp8 2.57 9.47E-05 12 Protein Tnks1bp1 Tnks1bp1 2.53 1.22E-04 13 Alpha-parvin Parva 2.47 1.78E-04 14 C4b-binding protein alpha chain C4bpa 2.42 2.53E-04 15 Protein KTI12 homolog Kti12 2.41 2.74E-04 16 Protein Rab11fip5 Rab11fip5 2.41 2.84E-04 17 Protein Mcpt1l3 Mcpt1l3 2.33 4.43E-04 18 Phospholipase B-like 1 Plbd1 2.33 4.76E-04 Aldehyde dehydrogenase (NAD), cytosolic 19 2.32 4.93E-04 (Fragments) 20 Protein Dpy19l2 Dpy19l2 2.3 5.68E-04 21 Regenerating islet-derived 3 alpha, isoform CRA_a Reg3a 2.27 6.74E-04 22 60S acidic ribosomal protein P1 Rplp1 2.26 7.22E-04 23 Serum albumin Alb 2.25 7.98E-04 24 Ribonuclease 4 Rnase4 2.24 8.25E-04 25 Cct-5 protein (Fragment) Cct5 2.24 8.52E-04 26 Protein S100-A9 S100a9 2.22 9.71E-04 27 Creatine kinase M-type Ckm 2.21 1.00E-03 28 Protein Larp4b Larp4b 2.18 1.25E-03
  • CSA B52HB:20 a Practical Handbook for Implementing CSA B52:18, Mechanical Refrigeration Code

    CSA B52HB:20 a Practical Handbook for Implementing CSA B52:18, Mechanical Refrigeration Code

    A practical handbook for implementing CSA B52:18, Mechanical refrigeration code CSA B52HB:20 Legal Notice This document is provided by the Canadian Standards Association (operating as “CSA Group”) as a convenience only. Disclaimer and exclusion of liability This document is provided without any representations, warranties, or conditions of any kind, express or implied, including, without limitation, implied warranties or conditions concerning this document’s fitness for a particular purpose or use, its merchantability, or its noninfringement of any third party’s intellectual property rights. CSA Group does not warrant the accuracy, completeness, or currency of any of the information published in this document. CSA Group makes no representations or warranties regarding this document’s compliance with any applicable statute, rule, or regulation. IN NO EVENT SHALL CSA GROUP, ITS VOLUNTEERS, MEMBERS, SUBSIDIARIES, OR AFFILIATED COMPANIES, OR THEIR EMPLOYEES, DIRECTORS, OR OFFICERS, BE LIABLE FOR ANY DIRECT, INDIRECT, OR INCIDENTAL DAMAGES, INJURY, LOSS, COSTS, OR EXPENSES, HOWSOEVER CAUSED, INCLUDING BUT NOT LIMITED TO SPECIAL OR CONSEQUENTIAL DAMAGES, LOST REVENUE, BUSINESS INTERRUPTION, LOST OR DAMAGED DATA, OR ANY OTHER COMMERCIAL OR ECONOMIC LOSS, WHETHER BASED IN CONTRACT, TORT (INCLUDING NEGLIGENCE), OR ANY OTHER THEORY OF LIABILITY, ARISING OUT OF OR RESULTING FROM ACCESS TO OR POSSESSION OR USE OF THIS DOCUMENT, EVEN IF CSA GROUP HAS BEEN ADVISED OF THE POSSIBILITY OF SUCH DAMAGES, INJURY, LOSS, COSTS, OR EXPENSES. In publishing and making this document available, CSA Group is not undertaking to render professional or other services for or on behalf of any person or entity or to perform any duty owed by any person or entity to another person or entity.
  • MALE Protein Name Accession Number Molecular Weight CP1 CP2 H1 H2 PDAC1 PDAC2 CP Mean H Mean PDAC Mean T-Test PDAC Vs. H T-Test

    MALE Protein Name Accession Number Molecular Weight CP1 CP2 H1 H2 PDAC1 PDAC2 CP Mean H Mean PDAC Mean T-Test PDAC Vs. H T-Test

    MALE t-test t-test Accession Molecular H PDAC PDAC vs. PDAC vs. Protein Name Number Weight CP1 CP2 H1 H2 PDAC1 PDAC2 CP Mean Mean Mean H CP PDAC/H PDAC/CP - 22 kDa protein IPI00219910 22 kDa 7 5 4 8 1 0 6 6 1 0.1126 0.0456 0.1 0.1 - Cold agglutinin FS-1 L-chain (Fragment) IPI00827773 12 kDa 32 39 34 26 53 57 36 30 55 0.0309 0.0388 1.8 1.5 - HRV Fab 027-VL (Fragment) IPI00827643 12 kDa 4 6 0 0 0 0 5 0 0 - 0.0574 - 0.0 - REV25-2 (Fragment) IPI00816794 15 kDa 8 12 5 7 8 9 10 6 8 0.2225 0.3844 1.3 0.8 A1BG Alpha-1B-glycoprotein precursor IPI00022895 54 kDa 115 109 106 112 111 100 112 109 105 0.6497 0.4138 1.0 0.9 A2M Alpha-2-macroglobulin precursor IPI00478003 163 kDa 62 63 86 72 14 18 63 79 16 0.0120 0.0019 0.2 0.3 ABCB1 Multidrug resistance protein 1 IPI00027481 141 kDa 41 46 23 26 52 64 43 25 58 0.0355 0.1660 2.4 1.3 ABHD14B Isoform 1 of Abhydrolase domain-containing proteinIPI00063827 14B 22 kDa 19 15 19 17 15 9 17 18 12 0.2502 0.3306 0.7 0.7 ABP1 Isoform 1 of Amiloride-sensitive amine oxidase [copper-containing]IPI00020982 precursor85 kDa 1 5 8 8 0 0 3 8 0 0.0001 0.2445 0.0 0.0 ACAN aggrecan isoform 2 precursor IPI00027377 250 kDa 38 30 17 28 34 24 34 22 29 0.4877 0.5109 1.3 0.8 ACE Isoform Somatic-1 of Angiotensin-converting enzyme, somaticIPI00437751 isoform precursor150 kDa 48 34 67 56 28 38 41 61 33 0.0600 0.4301 0.5 0.8 ACE2 Isoform 1 of Angiotensin-converting enzyme 2 precursorIPI00465187 92 kDa 11 16 20 30 4 5 13 25 5 0.0557 0.0847 0.2 0.4 ACO1 Cytoplasmic aconitate hydratase IPI00008485 98 kDa 2 2 0 0 0 0 2 0 0 - 0.0081 - 0.0
  • CSA) in and Around California’S Central Valley

    CSA) in and Around California’S Central Valley

    Community Supported Agriculture (CSA) in and around California’s Central Valley: Farm and Farmer Characteristics, Farm-Member Relationships, Economic Viability, Information Sources, and Emerging Issues Ryan E. Galt Assistant Professor Department of Human and Community Development & Agricultural Sustainability Institute Jessica Beckett M.Sc., Community Development Colleen C. Hiner Ph.D. Candidate, Geography Graduate Group Libby O’Sullivan Ph.D Student, Geography Graduate Group August 2011 University of California, Davis Table of Contents Executive Summary .......................................................................................................iii Acknowledgements ........................................................................................................v The recent expansion of Community Supported Agriculture .......................................1 Study details: study site, sample, methodology, and data analysis ...............................3 CSA farms and CSA farmers ..........................................................................................5 What kinds of CSAs exist? A typology for the region________________________ 6 When did CSAs start and where are they located? __________________________9 Who are CSA farmers and how did they become CSA farmers? ________________9 What are CSA farms like? ____________________________________________11 How is work organized in CSAs operations?______________________________ 14 The farm-member relationship ....................................................................................17
  • 4. Thermodynamics 4.1. Overview 4.2. Basic Concepts and Principles

    4. Thermodynamics 4.1. Overview 4.2. Basic Concepts and Principles

    4. Thermodynamics Tore Haug-Warberg, Long-Qing Chen, Ursula Kattner, Bengt Hallstedt, André Costa e Silva, Joonho Lee, Jean-Marc Joubert, Jean-Claude Crivello, Fan Zhang, Bethany Huseby, Olle Blomberg 4.1. Overview Thermodynamic modelling is software that uses thermodynamic calculations to predict the properties and behaviours of materials under various conditions. At its most basic, for example, thermodynamic modelling software provides information such as the melting point of an alloy, but in practice, the software is used to answer much more complicated and time-consuming questions about the behaviour of complex materials. Thermodynamic modelling is currently one of the most mature areas of ICME (Integrated Computational Materials Engineering), and companies that produce software tools for thermodynamic modelling are deeply involved in initiatives in the EU and US to advance the ICME vision, so thermodynamic modelling will likely continue to be an important part of many ICME projects. This chapter gives an overview of the current theory and practice of thermodynamic modelling. Sections 4.2 and 4.3 provide an introduction to some basic thermodynamic concepts and theory. Section 4.4 then gives an overview of the so-called CALPHAD (CALculation of Phase Diagrams) method, which is a thermodynamic modelling approach frequently used when it comes to solving practical material design problems that involve multi-component systems. In this approach, thermodynamic calculations provide the information on phases in stable or metastable equilibrium that are needed for predicting properties of materials under a wide range of temperature, pressure and composition conditions. Section 4.5 focuses on thermodynamic data, data formats and databases.
  • Plumbing Waste Fittings This Is a Preview of "CSA ASME A112.18.2-2..."

    Plumbing Waste Fittings This Is a Preview of "CSA ASME A112.18.2-2..."

    This is a preview of "CSA ASME A112.18.2-2...". Click here to purchase the full version from the ANSI store. ASME A112.18.2-2020/ CSA B125.2:20 National Standard of Canada American National Standard Plumbing waste fittings This is a preview of "CSA ASME A112.18.2-2...". Click here to purchase the full version from the ANSI store. Legal Notice for Harmonized Standard Jointly Developed by ASME and CSA Group Intellectual property rights and ownership As between American Society of Mechanical Engineers (“ASME”) and Canadian Standards Association (Operating as “CSA Group”) (collectively “ASME and CSA Group”) and the users of this document (whether it be in printed or electronic form), ASME and CSA Group are the joint owners of all works contained herein that are protected by copyright, all trade-marks (except as otherwise noted to the contrary), and all inventions and trade secrets that may be contained in this document, whether or not such inventions and trade secrets are protected by patents and applications for patents. The unauthorized use, modification, copying, or disclosure of this document may violate laws that protect the intellectual property of ASME and CSA Group and may give rise to a right in ASME and CSA Group to seek legal redress for such use, modification, copying, or disclosure. ASME and CSA Group reserve all intellectual property rights in this document. Disclaimer and exclusion of liability This document is provided without any representations, warranties, or conditions of any kind, express or implied, including, without limitation, implied warranties or conditions concerning this document’s fitness for a particular purpose or use, its merchantability, or its non-infringement of any third party’s intellectual property rights.
  • Journal of Environment and Health Sciences

    Journal of Environment and Health Sciences

    Journal of Environment and Health Sciences Review Article Organophosphorus Flame Retardants (OPFR): Neurotoxicity Mohamed B. Abou-Donia1* Mohamed Salama2, Mohamed Elgamal2, Islam Elkholi2,3, Qiangwei Wang1,4 1Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, USA 2Medical Experimental Research Center (MERC), Faculty of Medicine, Mansoura University, Mansoura, Egypt 3Center for Aging and Associated Diseases (CAAD), Zewail City of Science and Technology, Giza 4Zhejiang University, China *Corresponding author: Mohamed B. Abou-Donia, Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 277, USA, Tel: +919-68422/ Fax: 919-681-822, E-mail: [email protected] Citation: Abou-Donia, M.B., et al. Organophosphorus Flame Retardants (OPFR): Neurotoxicity. (2016) J Environ Health Sci 2(1): 1- 30 Received date: July 07, 2015 Accepted date: May 05, 2016 DOI: 10.15436/2378-6841.16.022 Published date: May 11, 2016 Abstract Organophosphorus flame retardants (OPFRs) are used as additives in plasticizers, foams, hydraulic fluids, anti-foam agents, and coatings for electronic components/devices to inhibit flames. These chemicals were developed and used as flame re- tardants because of environmental and health concerns of previously used brominated and chlorinated flame retardants (FRs). OPCFRs are divided into five main groups: organophosphates, organophosphonates, organophosphinates, organoposphine oxide, and organophosphites. Most of OPFRs are organophosphate esters that are further classified into the following five groups: 1. Ali- phatic, 2. Brominated aliphatic, 3. Chlorinated aliphatic, 4. Aromatic-aliphatic, and 5. Aromatic phosphates. These OPFRs have the following neurotoxic actions: 1. Cholinergic Neurotoxicity, 2. Organophosphate-Induced Delayed Neurotoxicity (OPIDN), and 3.