Biophysical Models for Prediction of Activity and ADME Parameters: Application to Quinolone Antibiotics
|
|
|
- Barnaby Smith
- 6 years ago
- Views:
Transcription
1 Moleculr Biophrmceutics. Hwii Biophysicl Models for Prediction of Activity nd ADME Prmeters: Appliction to Quinolone Antibiotics Mª del Vl Bermejo Snz, Ph.D. Associte Professor of Phrmceutics Depto. rmci cultd de rmci. Universidd de Vlenci Espñ Moleculr Biophrmceutics. Hwii utline Biophysicl bsorption models Plsm QSAR methods in drug bsorption nd ctivity. CH C CH :.96 C6 C4 C C7.4 C.4C.8C CH.4 *C :.. S.8 rl bsorption prediction in drug development Lumen Concentrtion (µg/ml) Bolus rl. 4 Time (min)
2 Moleculr Biophrmceutics. Hwii Closed Loop Perfusion Technique: Doluisio s method Absorption rte coefficient: Permebility vlues A = A e k t c k R Peff = Syringe Stopcock Smples Drug in SLUTI Bile duct closed Wter rebsorption mesurement Gut Cnnul Moleculr Biophrmceutics. Hwii Closed Loop Perfusion Technique: Doluisio s method Absorption rte constnt: Permebility vlues A = A e k t c k R Peff = Concentrtion (µg/ml) Time (min - ) 4
3 Moleculr Biophrmceutics. Hwii Biophysicl Absorption Models: Plá-Delfin nd Moreno k Smll Intestine lumen k queous pthwy membrne k lumen k Colon Aqueous lyer membrne Plsm k Aqueous lyer Plsm km P K = B + P kp C + d C + P k km P K = B + P lipophilicity Lipophilicity Absorption rte coeffiecient h - Crbmtes n-ctnol Prtition coeffcient Phenyllkylmines Moleculr Biophrmceutics. Hwii Smll intestine Absorption rte coefficient h- Ring-Anilines n-ctnol Prtition Coefficient Sulfonmides MW> D Absorption rte coefficient h- 4 Absorption rte coefficient h - 4. Chromtogrphic constnts. Chromtogrphic constnt 6
4 Moleculr Biophrmceutics. Hwii Colon Absorption rte coefficient h Phenyl-lkyl cids. HPLC, Cpcity fctor K' Absorption rte coefficient h - Ring-Anilines 4 Distribution coefficient 7 Moleculr Biophrmceutics. Hwii Biophysicl Absorption Models: Plá-Delfin nd Moreno Gstric bsorption rte constnt, h -, (CH ) n CH n=-7 Distribution Coefficient, D ph:. 8 4
5 Moleculr Biophrmceutics. Hwii Biophysicl Absorption Models: Plá-Delfin nd Moreno Gstric mucos Lumen queous lyer Plsm k P Phospholipids Glycoclyx Membrne d C P k = f + E P 9 Moleculr Biophrmceutics. Hwii TAURCHLATE: ITERPRETATI ITS ULCERGEIC EECT. queous Lumen Plsm lyer Gstric bsorption constnt h - ko k Distribution Coefficient (n-ctnol) Lumen queous lyer Glycoclyx Membrne Plsm Phospholipids Glycoclyx Membrne
6 Moleculr Biophrmceutics. Hwii Biophysicl Absorption Models: Summry Stomch Smll Intestine Colon Lumen queous lyer Plsm Phospholipids Membrne Glycoclyx k lumen k k k Aqueous lyer membrne Plsm k lumen k Aqueous lyer k membrne Plsm P d C P k = + E P f km P K = B + P P kp C + d C + P P km P K = B + P Moleculr Biophrmceutics. Hwii Biophysicl Absorption Models: Summry Stomch Smll Intestine: MW> D Colon Lumen queous lyer Plsm lumen k membrne k lumen k membrne Phospholipids Membrne Glycoclyx k k Aqueous lyer Plsm Aqueous lyer k Plsm P d C P k = + E P f P km P K = B + P P km P K = B + P 6
7 Moleculr Biophrmceutics. Hwii Biophysicl Absorption Models: Plá-Delfin nd Moreno CH CH R R R= H, orfloxcin R= H, Ciprofloxcin R= CH, CH -(CH ) n - n=- CEAVISA S.A. Spin Moleculr Biophrmceutics. Hwii Biophysicl Absorption Models: Plá-Delfin nd Moreno Absorption rte constnt h orfloxcin.. Prtition coefficient, P Absorption rte constnt h Ciprofloxcin.. Prtition coefficient, P 4 7
8 Absorption rte constnt h - lumen K. membrne kq Moleculr Biophrmceutics. Hwii d Aq. lyer Plsm C P k = = + + E MW P d k kq kmem kmem... Prtition coefficient, P Kq (h - ) Kmem (h - ) Moleculr Biophrmceutics. Hwii QSAR methodologies in drug bsorption CH lumequine CH CH S CEAVISA 884 CEAVISA
9 Moleculr Biophrmceutics. Hwii QSAR methodologies in drug bsorption ITDYS. Université Pris VII. rnce. Prof. Christine Mercier.e-4.e-4 CV 884 lumequine CV 899 P eff (cm/s).e-4.e- orfloxcin derivtives Ciprofloxcin derivtives. x - x - x - x x x x x x x 6 n-ctnol Prtition Coefficient 7 Moleculr Biophrmceutics. Hwii QSAR methodologies in drug bsorption ITDYS. Université Pris VII: Vizet P. PATQSAR. Version CH -CH CH -CH -CH -CH Trze CH -CH-CH CH -A-B-C A B Vector A A B B C Vizet P. PATQSAR. Version
10 Moleculr Biophrmceutics. Hwii Compounds BER BER BER BER4 BER BER6 BER7 BER8 BER9 BER BER BER BER BER4 BER BER6 EW EW EW4 EW Log K exp Log K clc Dependent vrible Log K diff E V V V4 Topologicl mtrix V EQ(V6;V7; V8) 9 Moleculr Biophrmceutics. Hwii QSAR methodologies in drug bsorption.4c 7.4C 6.4 C.C 6.4C 4.4C Lipophilicity-structure correltion.4c 4. C 7.C.4C Absorption-structure correltion.7c. C CH.8C.4C. C CH.64C S S CH CH.4 Log P.6 CH Log k CH :.96 *C :. :.8
11 Moleculr Biophrmceutics. Hwii QSAR methodologies in drug bsorption E.Coli Stph. CH -.8 C C -.8 C. C o :.. C C C CH.6 CH -.8 C C -.8 C. C o :. -.8 C C 4. C CH.8 Structure- ntibcteril ctivity correltion Log /CMI Moleculr Biophrmceutics. Hwii Quinolone Topoisomerse
12 Moleculr Biophrmceutics. Hwii Experimentl Log P 4 - R = Predicted Log P Experimentl Log K R = Predicted Log K Experimentl Log /Mic E. Coli Predicted Log /Mic E. Coli R =.96 Experimentl Log /Mic Stph R = Predicted Log /Mic Stph. Moleculr Biophrmceutics. Hwii. Lipophilicity is the min fctor governing quinolone bsorption.. The bsorption-prtition reltionship hs good predictive performnce of intestinl permebility.. The ntibcteril ctivity is decresed by the lkyl chin which hinders the ccess to the bcteril topoisomerse or drug binding to DA. 4
13 Moleculr Biophrmceutics. Hwii CH CH R R R= H, orfloxcin CH CH R me H CV 97 -CH CV 97 R -CH -CH -(CH ) -CH CV 97 CV 97 R= H, Ciprofloxcin -(CH ) -CH CV 974 R= CH, CH -(CH ) n - n=- Homologous Compounds CEAVISA S.A. Spin Moleculr Biophrmceutics. Hwii CV97X derivtives.e-4 Peff (cm/s).e-4 CV97 CV974 CV97.e- CV97. CV n-ctnol Prtition coefficient 6
14 Moleculr Biophrmceutics. Hwii CV97X derivtives.e-4 Peff (cm/s).e-4 CV97 CV974 CV97.e- CV97. CV n-ctnol Prtition coefficient 7 Moleculr Biophrmceutics. Hwii P-gp levels e- Permebility cm/s e- e- e- e- e-6 CV97 conc. µg/ml.. Intest. IleumColonWhole Jejunum Duodenum 8 4
15 Permebility cm/s Moleculr Biophrmceutics. Hwii.e-.e-.e-.e-.e-.e-.e-6 CV97 conc. µg/ml... Intest. IleumColonWhole Jejunum Duodenum 9 Moleculr Biophrmceutics. Hwii.e-.e-.e-.e- Permebility cm/s.e-.e-.e-6 CV97 conc. µg/ml... D J Ileum Whole Intest.
16 Permebility cm/s Moleculr Biophrmceutics. Hwii.e-.e-.e-.e-.e-.e-.e-6. CV97 conc. µg/ml.. C Ileum D J +Verpmil Whole Intest. Moleculr Biophrmceutics. Hwii Model ssumptions Pdiff unchnged long GI trct. Efflux system Km vlue (ffinity) is unchnged long GI trct. Vm= f(expression level). Ileum 6
17 Moleculr Biophrmceutics. Hwii Concentrtion (µg/ml).. Time (min) Vm (nmol s- cm-) Whole intestine Km (µm) Prmeter Pdiff(cm s-) Vm (nmol s- cm-) ileum Whole intestine dc Vmx C = ( Pdiff ) C+ dt R R Km + C Ileum dc Vmx b C = ( Pd if f ) C+ dt R R K + C b b m In situ study Vlue (SD).7 - (. - ).6-4 (.76-4 ).94-4 (.6-4 ).94 (8.) Moleculr Biophrmceutics. Hwii. CV97 shows sturble efflux process verpmil sensitive. 4. The quinolone effective permebility is lower in rt ileum due to the higher P-glycoprotein expression level. 4 7
18 Moleculr Biophrmceutics. Hwii = ( E g ) ( Eh) E g = gut first-pss effects E h = liver first-pss effects rl bsorption prediction in drug development Biovilbility prediction in drug development: fluoroquinolones. CICYT (SA 96-7) Director. Prof. Plá-Delfin Moleculr Biophrmceutics. Hwii rl bsorption prediction in drug development = ( E g ) ( Eh) k T = e ( P T eff = e R res ) ( A ) n = e ( ) res T T bs = e 6 8
19 Moleculr Biophrmceutics. Hwii rl bsorption prediction in drug development Administrtion (I.V.) Blood Smples Cnnul jugulr Vein rl Administrtion 7 Moleculr Biophrmceutics. Hwii rl bsorption prediction in drug development rl dministrtion Group A (8- rts) I.V dministrtion (bolus or perfusion) Group B (8- rts) Plsm smpling nd Anlysis AUC clcultion AUC t + AUC t (Trpezoidl rule) ( C t /k) PK Popultion nlysis: onmem v.. Post-hoc Byesin ind. prmeter estimtion 8 9
20 Moleculr Biophrmceutics. Hwii orfloxcin plsm levels (mg/l). () D iv = mg D orl =4 mg. 4 Time (min) Ciprofloxcin plsm levels (mg/l).. 4 Time (min) D iv =4 mg D orl =4 mg 9 Moleculr Biophrmceutics. Hwii 4'- Propyl-ciprofloxcin plsm levels(mg/l). () D iv =4 mg D orl =4 mg. 4 Time (min) Pefloxcin plsm levels (mg/l). () D iv =8 mg D orl =8 mg. 4 6 Time (min) 4
21 Moleculr Biophrmceutics. Hwii.. = e CV97 k.4 CV97 Propil-or Propil-Cipro lumequine in vivo.8.6 Pefloxcin CV97 CV97 CV974.4 Ciprofloxcin orfloxcin k in situ 4 Moleculr Biophrmceutics. Hwii = e Experimentl k.4 b[]=. b[]=.96 r ²= Predicted 4
22 Moleculr Biophrmceutics. Hwii Cldis=k Vc R =.674 Cl=k Vc R = Vc R =. Vp R = Moleculr Biophrmceutics. Hwii 4. The in situ intestinl permebility is good predictive prmeter of in vivo.. The sturble (efflux nd bsorption) processes observed in situ (nd in vitro) hd not significnt influence in vivo in rts t the orl doses used. 6. Disposition prmeters still under modelling 44
23 Moleculr Biophrmceutics. Hwii Model construction ATP ATP ADP+P ATP synthesis Pssive SAz complex difussion Electron trnsport complexes Kd Kout [ATP] Kin Active ATP levels trnsport ATP Vm p; Km ATP consume SAz ADP+P Trnsporter Moleculr mechnisms. d[ ATP] = kin kout [ ATP] dt d[ ATP] = kin kout [ ATP] = dt [ ATP] = kin = kout kinp [ SAz] = kin C + [ SAz] Dt fitting K (h - ) ATP frction Srfloxcin Conc.4. mm.. mm mm. 4 6 Time [min] predictions 4 Moleculr Biophrmceutics. Hwii Acknowledgments An Virgini Crlos Isbel González Crlos ernández Vicente Csbó Virgini Merino An Ruiz Isbel Vicente unds: Generlitt Vlencin (GV ) MEC (SA 96 7) Compounds: Dr. Jon reixs CEAVISA SA 46
Prediction of Oral Absorption: 6-Fluoroquinolones
Prediction of ral Absorption: 6-luoroquinolones Mª del Val Bermejo Sanz, Ph.D. Depto. armacia y Tecnología armacéutica acultad de armacia. Universidad de Valencia Valencia, España Strategies for ral Drug
Department of Physical Pharmacy and Pharmacokinetics Poznań University of Medical Sciences Pharmacokinetics laboratory
Deprtment of Physicl Phrmcy nd Phrmcoinetics Poznń University of Medicl Sciences Phrmcoinetics lbortory Experiment 1 Phrmcoinetics of ibuprofen s n exmple of the first-order inetics in n open one-comprtment
Organic Acids & Bases pk a Values. ESE/CH 176 Environmental Physical Organic Chemistry April 2018
Orgnic Acids & Bses pk Vlues ESE/CH 176 Environmentl Physicl Orgnic Chemistry 23-27 April 2018 Wter Dissocition Rection: K + - H2O ¾¾ ¾¾ H + OH K + - HO 2 + HO 2 ¾¾ ¾¾ HO 3 + OH Mss Action Lw K = g H +
13: Diffusion in 2 Energy Groups
3: Diffusion in Energy Groups B. Rouben McMster University Course EP 4D3/6D3 Nucler Rector Anlysis (Rector Physics) 5 Sept.-Dec. 5 September Contents We study the diffusion eqution in two energy groups
Supplementary Information
Supplementry Informtion Coopertion of locl motions in the Hsp90 moleculr chperone ATPse mechnism Andre Schulze 1, Gerti Beliu 1, Dominic A. Helmerich 1, Jonthn Schubert 1, Lurence H. Perl 2, Chrisostomos
Factors affecting the phonation threshold pressure and frequency
3SC Fctors ffecting the phontion threshold pressure nd frequency Zhoyn Zhng School of Medicine, University of Cliforni Los Angeles, CA, USA My, 9 57 th ASA Meeting, Portlnd, Oregon Acknowledgment: Reserch
temperature is known as ionic product of water. It is designated as K w. Value of K w
Ionic product of ter The product of concentrtions of H nd OH ions in ter t prticulr temperture is knon s ionic product of ter. It is designted s K. H O H 1 OH ; H 57.3 kjm The vlue of [H ][OH ] K ; K[HO]
Black oils Correlations Comparative Study
Reservoir Technologies Blck oils Correltions Comprtive Study Dr. Muhmmd Al-Mrhoun, Mnging Director Sturdy, 26 April, 2014 Copyright 2008, NExT, All rights reserved Blck oils Correltions Introduction to
GI Simulation Methods
Gastrointestinal Simulation Based on the Advanced Compartmental Absorption and Transit (ACAT) Michael B. Bolger, Ph.D. Founding Scientist Simulations Plus, Inc. GI Simulation Methods Dispersion Model Ho,
Fundamentals of Analytical Chemistry
Homework Fundmentls of nlyticl hemistry hpter 9 0, 1, 5, 7, 9 cids, Bses, nd hpter 9(b) Definitions cid Releses H ions in wter (rrhenius) Proton donor (Bronsted( Lowry) Electron-pir cceptor (Lewis) hrcteristic
Deriving hydraulic conductivity function from soil column tests
Deriving hydrulic conductivity function from soil column tests Yvonne Lins, Mri Dtchev & Tom Schnz DFG Fo 444 - TP 4 Experimentelle und theoretische Untersuchungen teilgesättigter Reibungsmterilien Content
The general concept of pharmacokinetics
The general concept of pharmacokinetics Hartmut Derendorf, PhD University of Florida Pharmacokinetics the time course of drug and metabolite concentrations in the body Pharmacokinetics helps to optimize
Antibiotic efflux pumps in eucaryotic cells: consequences for activity against intracellular bacteria
Antibiotic efflux pumps in eucaryotic cells: consequences for activity against intracellular bacteria Françoise Van Bambeke on behalf of J.M. Michot, C. Seral, M. Heremans, M.P. Mingeot-Leclercq, P.M.
Case Study VI Answers PHA 5127 Fall 2006
Qustion. A ptint is givn 250 mg immit-rls thophyllin tblt (Tblt A). A wk ltr, th sm ptint is givn 250 mg sustin-rls thophyllin tblt (Tblt B). Th tblts follow on-comprtmntl mol n hv first-orr bsorption
Module 2: Rate Law & Stoichiomtery (Chapter 3, Fogler)
CHE 309: Chemicl Rection Engineering Lecture-8 Module 2: Rte Lw & Stoichiomtery (Chpter 3, Fogler) Topics to be covered in tody s lecture Thermodynmics nd Kinetics Rection rtes for reversible rections
Math 31S. Rumbos Fall Solutions to Assignment #16
Mth 31S. Rumbos Fll 2016 1 Solutions to Assignment #16 1. Logistic Growth 1. Suppose tht the growth of certin niml popultion is governed by the differentil eqution 1000 dn N dt = 100 N, (1) where N(t)
( dg. ) 2 dt. + dt. dt j + dh. + dt. r(t) dt. Comparing this equation with the one listed above for the length of see that
Arc Length of Curves in Three Dimensionl Spce If the vector function r(t) f(t) i + g(t) j + h(t) k trces out the curve C s t vries, we cn mesure distnces long C using formul nerly identicl to one tht we
Physical Chemistry I for Biochemists Chem340. Lecture 38 (4/20/11) Yoshitaka Ishii. Announcement
Physicl Chemistry I for Biochemists Chem34 Lecture 38 (4//11) Yoshitk Ishii Ch. 9.7 9.1 9.1 Announcement HW1 due dte is 4/7 (Wed) Exm 3 will be returned probbly this Fridy Finl Exm 5/4 (Wed) 1 3 pm Quiz
CHAPTER 08: MONOPROTIC ACID-BASE EQUILIBRIA
Hrris: Quntittive Chemicl Anlysis, Eight Edition CHAPTER 08: MONOPROTIC ACIDBASE EQUILIBRIA CHAPTER 08: Opener A CHAPTER 08: Opener B CHAPTER 08: Opener C CHAPTER 08: Opener D CHAPTER 08: Opener E Chpter
Dissolution stability of a modified release product
Dissolution stility of modified relese product nd MBSW My 9, 9 Dvid.LeBlond@ott.com Outline Multivrite dt set Mixed model (sttic view) Hierrchicl model (dynmic view) Why Byesin pproch? Selecting priors
Dissociation of a ferric maltol complex and its subsequent metabolism during absorption across the small intestine of the
Br. J. Phrmcol. (1991), 12, 723-729,'-. Mcmilln Press Ltd, 1991 Dissocition of ferric mltol complex nd its subsequent metbolism during bsorption cross the smll intestine of the rt 'Mrgery A. Brrnd, Brin
Rates of chemical reactions
Rtes of chemicl rections Mesuring rtes of chemicl rections Experimentl mesuring progress of the rection Monitoring pressure in the rection involving gses 2 NO( g) 4 NO ( g) + O ( g) 2 5 2 2 n(1 α) 2αn
Post-operative absorption of water from the small intestine
Gut, 19,, 8 Post-opertive bsorption of wter from the smll intestine L. F. TINCKLR AND W. KULK From the Deprtment of Surgery, University of Liverpool, nd Liverpool Rdium Institute DITORIAL SYNOPSIS An investigtion
Amyloidogenesis highlighted by designed peptides forming supramolecular self-assemblies
Electronic Supplementry nformtion Amyloidogenesis highlighted y designed peptides forming suprmoleculr self-ssemlies M. ueri,. T. Dolphin, P. Dumy, nd J. rci* Déprtement de Chimie Moléculire, UM-CNS 5250,
Drug dissolution testing is an integral part of
dx.doi.org/10.14227/dt220415p22 Design nd Evlution of Novel Bio-Mimicking In Vitro Dissolution Test Apprtus for Floting Drug Delivery Systems L. Bldniy 1,*, S. Sisivm 2, nd M. Gohel 1 1 Deprtment of Phrmceuticl
Interpreting Integrals and the Fundamental Theorem
Interpreting Integrls nd the Fundmentl Theorem Tody, we go further in interpreting the mening of the definite integrl. Using Units to Aid Interprettion We lredy know tht if f(t) is the rte of chnge of
Muscle and serum acylcarnitine profiles in dairy cows during the periparturient period
Muscle nd serum cylcrnitine profiles in diry cows during the periprturient period Y. Yng, 1 C. Prehn, 2 J. Admski, 2 J. Rehge, 3 S. Dänicke, 4 H. Suerwein, 1 H. Sdri 1 1 Institute of Animl Science, Physiology
Probabilistic Investigation of Sensitivities of Advanced Test- Analysis Model Correlation Methods
Probbilistic Investigtion of Sensitivities of Advnced Test- Anlysis Model Correltion Methods Liz Bergmn, Mtthew S. Allen, nd Dniel C. Kmmer Dept. of Engineering Physics University of Wisconsin-Mdison Rndll
Chapter 1. Chapter 1 1
Chpter Chpter : Signls nd Systems... 2. Introduction... 2.2 Signls... 3.2. Smpling... 4.2.2 Periodic Signls... 0.2.3 Discrete-Time Sinusoidl Signls... 2.2.4 Rel Exponentil Signls... 5.2.5 Complex Exponentil
+ x 2 dω 2 = c 2 dt 2 +a(t) [ 2 dr 2 + S 1 κx 2 /R0
Notes for Cosmology course, fll 2005 Cosmic Dynmics Prelude [ ds 2 = c 2 dt 2 +(t) 2 dx 2 ] + x 2 dω 2 = c 2 dt 2 +(t) [ 2 dr 2 + S 1 κx 2 /R0 2 κ (r) 2 dω 2] nd x = S κ (r) = r, R 0 sin(r/r 0 ), R 0 sinh(r/r
Time in Seconds Speed in ft/sec (a) Sketch a possible graph for this function.
4. Are under Curve A cr is trveling so tht its speed is never decresing during 1-second intervl. The speed t vrious moments in time is listed in the tle elow. Time in Seconds 3 6 9 1 Speed in t/sec 3 37
CHM Physical Chemistry I Chapter 1 - Supplementary Material
CHM 3410 - Physicl Chemistry I Chpter 1 - Supplementry Mteril For review of some bsic concepts in mth, see Atkins "Mthemticl Bckground 1 (pp 59-6), nd "Mthemticl Bckground " (pp 109-111). 1. Derivtion
Research Project Summary
Environmentl Assessment nd Risk Anlysis Element Reserch Project Summry June 11,2002 A SCREENING MODEL FOR PREDICTING CONCENTRATIONS OF VOLATILE ORGANIC CHEMICALS IN SHOWER STALL AIR Pul F. Snders, Ph.D.
6. Photoionization of acridine through singlet and triplet channels
Chpter 6: Photoioniztion of cridine through singlet nd triplet chnnels 59 6. Photoioniztion of cridine through singlet nd triplet chnnels Photoioinztion of cridine (Ac) in queous micelles hs not yet een
DISSOLUTION RATE LIMITING AUC: SIMPLE METHODOLOGY FOR MEASURING DISSOLUTION RATE OF THE ENTIRE DOSE IN BIORELEVANT MEDIA
DISSOLUTION RATE LIMITING AUC: SIMPLE METHODOLOGY FOR MEASURING DISSOLUTION RATE OF THE ENTIRE DOSE IN BIORELEVANT MEDIA Jesse Kuiper and Paul Harmon Outline 2 Understanding the path to absorption (and
UNIVERSITY OF MALTA DEPARTMENT OF CHEMISTRY. CH237 - Chemical Thermodynamics and Kinetics. Tutorial Sheet VIII
UNIVERSITY OF MALTA DEPARTMENT OF CHEMISTRY CH237 - Chemicl Thermodynmics nd Kinetics Tutoril Sheet VIII 1 () (i) The rte of the rection A + 2B 3C + D ws reported s 1.0 mol L -1 s -1. Stte the rtes of
u( t) + K 2 ( ) = 1 t > 0 Analyzing Damped Oscillations Problem (Meador, example 2-18, pp 44-48): Determine the equation of the following graph.
nlyzing Dmped Oscilltions Prolem (Medor, exmple 2-18, pp 44-48): Determine the eqution of the following grph. The eqution is ssumed to e of the following form f ( t) = K 1 u( t) + K 2 e!"t sin (#t + $
Population bottleneck : dramatic reduction of population size followed by rapid expansion,
Selection We hve defined nucleotide diversity denoted by π s the proportion of nucleotides tht differ between two rndomly chosen sequences. We hve shown tht E[π] = θ = 4 e µ where µ cn be estimted directly.
TK Solver Case Study: Pharmacokinetics
TK Solver Case Study: Pharmacokinetics The content for this example was provided by Professor Prasad Dhurjati of the University of Delaware. It is used there in the class Applied Mathematics for Chemical
Antibiotic efflux pumps in eucaryotic cells: consequences for activity against intracellular bacteria
Antibiotic efflux pumps in eucaryotic cells: consequences for activity against intracellular bacteria Unité de Pharmacologie cellulaire et moléculaire F. Van Bambeke Magic bullets need to reach their target
Thermodynamics of the hydrophobic effect. I. Coupling of aggregation and p Ka
Biophysicl Chemistry 93 2001 3751 Thermodynmics of the hydrophobic effect. I. Coupling of ggregtion nd p K shifts in solutions of liphtic mines Dumnts Mtulis, Victor A. Bloomfield Deprtment of Biochemistry,
A. Limits - L Hopital s Rule ( ) How to find it: Try and find limits by traditional methods (plugging in). If you get 0 0 or!!, apply C.! 1 6 C.
A. Limits - L Hopitl s Rule Wht you re finding: L Hopitl s Rule is used to find limits of the form f ( x) lim where lim f x x! c g x ( ) = or lim f ( x) = limg( x) = ". ( ) x! c limg( x) = 0 x! c x! c
(Received 27 October 1998; Accepted 30 March 1999)
Environmentl Toxicology nd Chemistry, Vol. 18, No. 12, pp. 2723 2728, 1999 1999 SETAC Printed in the USA 0730-7268/99 $9.00.00 COMPARISON OF FOUR METHODS OF PREDICTING NEWLY MEASURED OCTANOL/WATER COEFFICIENTS
Why is it so hard to discover develop antibacterial drugs for Gram negative bacteria? Lynn L. Silver, Ph.D. LL Silver Consulting, LLC
Why is it so hard to discover develop antibacterial drugs for Gram negative bacteria? Lynn L. Silver, Ph.D. LL Silver Consulting, LLC 2 The Innovation gap in novel classes Obscures the Discovery void 1940
Chapter 9: Inferences based on Two samples: Confidence intervals and tests of hypotheses
Chpter 9: Inferences bsed on Two smples: Confidence intervls nd tests of hypotheses 9.1 The trget prmeter : difference between two popultion mens : difference between two popultion proportions : rtio of
Data Assimilation. Alan O Neill Data Assimilation Research Centre University of Reading
Dt Assimiltion Aln O Neill Dt Assimiltion Reserch Centre University of Reding Contents Motivtion Univrite sclr dt ssimiltion Multivrite vector dt ssimiltion Optiml Interpoltion BLUE 3d-Vritionl Method
Organic Acids - Carboxylic Acids
Orgnic Acids - rboxylic Acids Orgnic cids - crboxylic cid functionl group rboxylic cids re redily deprotonted by bses such s NO eg 3 O O - + O - + O 3 O O Acid Bse onjugte Bse onjugte Acid This rection
Supplementary Figure 1
Supplementry Figure (nesthetized) (wke) Normlized mplitude.5 Pek width (ms).6.4.2 4 2 2 x 3 Wveform slope Normlized mplitude.5 Pek width (ms).6.4.2 x 3 3 2 Wveform slope c (nesthetized) d (wke) Normlized
CHEMICAL KINETICS
CHEMICAL KINETICS Long Answer Questions: 1. Explin the following terms with suitble exmples ) Averge rte of Rection b) Slow nd Fst Rections c) Order of Rection d) Moleculrity of Rection e) Activtion Energy
(i) b b. (ii) (iii) (vi) b. P a g e Exponential Functions 1. Properties of Exponents: Ex1. Solve the following equation
P g e 30 4.2 Eponentil Functions 1. Properties of Eponents: (i) (iii) (iv) (v) (vi) 1 If 1, 0 1, nd 1, then E1. Solve the following eqution 4 3. 1 2 89 8(2 ) 7 Definition: The eponentil function with se
SCHEME OF WORK FOR IB MATHS STANDARD LEVEL
Snnrpsgymnsiet Lott Hydén Mthemtics, Stndrd Level Curriculum SCHEME OF WORK FOR IB MATHS STANDARD LEVEL Min resource: Mthemtics for the interntionl student, Mthemtics SL, Hese PART 1 Sequences nd Series
CALCULATION OF TIME CONSTANTS FOR
CALCULATON OF TME CONSTANTS FOR NTRACELLULAR DFFUSON N WHOLE CELL PATCH CLAMP CONFGURATON CARLOS OLVA, RA S. COHEN, AND RCHARD T. MATHAS Deprtment ofphysiology nd Biophysics, Stte University ofnew York
Student Activity 3: Single Factor ANOVA
MATH 40 Student Activity 3: Single Fctor ANOVA Some Bsic Concepts In designed experiment, two or more tretments, or combintions of tretments, is pplied to experimentl units The number of tretments, whether
Analysis on Parameters of Regeneration Subsystem in Liquid Desiccant Dehumidification Systems
Purdue University Purdue e-pubs Interntionl Refrigertion nd Air Conditioning Conference School of Mechnicl Engineering 2014 Anlysis on Prmeters of Regenertion Subsystem in Liquid Desiccnt Dehumidifiction
Simulations of the irradiation and temperature dependence of the efficiency of tandem photoelectrochemical water-splitting systems
SUPPORTING INFORMATION FOR Simultions of the irrdition nd temperture dependence of the efficiency of tndem photoelectrochemicl wter-splitting systems Sophi Hussener, Shu Hu, Chengxing Xing, Adm Z. Weber,
Isobaric vapor liquid equilibria of three aromatic hydrocarbon-tetraethylene glycol binary systems
Ž. Fluid Phse Equilibri 157 1999 299 307 Isobric vpor liquid equilibri of three romtic hydrocrbon-tetrethylene glycol binry systems Yng-Xin Yu ), Jin-Gng Liu, Gung-Hu Go Deprtment of Chemicl Engineering,
Flow of information in a drug discovery pipeline. 7th lecture Modern Methods in Drug Discovery WS16/17 1
Flow of information in a drug discovery pipeline 7th lecture Modern Methods in Drug Discovery WS16/17 1 eadmet prediction early Absorption Distribution Metabolism Elimination Toxicology Pharmacokinetic
Chapter 15. Applications of Aqueous Equlibria. A bag of mostly water - Star Trek -
Chpter 15. Applictions of Aqueous Equlibri A bg of mostly wter - Str Trek - Solutions of Acids or Bses Contining Common Ion Until now, we were concerned with the equilibrium of solution with n cid or bse.
Exponentials & Logarithms Unit 8
U n i t 8 AdvF Dte: Nme: Eponentils & Logrithms Unit 8 Tenttive TEST dte Big ide/lerning Gols This unit begins with the review of eponent lws, solving eponentil equtions (by mtching bses method nd tril
1 Error Analysis of Simple Rules for Numerical Integration
cs41: introduction to numericl nlysis 11/16/10 Lecture 19: Numericl Integrtion II Instructor: Professor Amos Ron Scries: Mrk Cowlishw, Nthnel Fillmore 1 Error Anlysis of Simple Rules for Numericl Integrtion
AMPERE CONGRESS AMPERE on Magnetic Resonance and Related Phenomena. Under the auspices of The GROUPEMENT AMPERE
AMPERE 2000 th 30 CONGRESS AMPERE on Mgnetic Resonnce nd Relted Phenomen Lison, Portugl, 23-2 July 2000 Under the uspices of The GROUPEMENT AMPERE Edited y: A.F. MARTINS, A.G. FEIO nd J.G. MOURA Sponsoring
Carbon foam impregnated with Phase Change Material (PCM) as a thermal barrier
Crbon fom impregnted with Phse Chnge Mteril (PCM) s therml brrier Osm Meslhy 1, Khlid Lfdi 1,2, nd Ahmed Elgfy 1 1 University of Dyton Reserch Institute, 300 College Prk, Dyton OH. 45469 USA 2 AFRL/MLBC,
Quantitative estimation of transmembrane ion transport in rat renal collecting duct principal cells
Gen. Physiol. Biophys. (2014), 33, 13 28 13 doi: 10.4149/gpb_2013063 Quntittive estimtion of trnsmembrne ion trnsport rt renl collectg duct prcipl cells Alexnder V. Ilysk 1, Denis I. rpov 2, Dmitriy A.
MODELLING OF MAGNESIUM OXIDE APPLICATION FOR STRUVITE PRECIPITATION
MDELLING F MAGNESIUM XIDE APPLIATIN FR STRUVITE PREIPITATIN J. Mzierski * nd S. Połwski ** * Polish Acdemy of Science, Institute of Environmentl Engineering, ul. M. Skłodowskiej-urie, -89 Zbrze, Polnd
Which of the following describes the net ionic reaction for the hydrolysis. Which of the following salts will produce a solution with the highest ph?
95. Which of the following descries the net ionic rection for the hydrolysis of NH4Cl( s)? A. NH4 ( q) Cl & ( q) NH4Cl( s) B. NH Cl & 4 ( s) NH4 ( q) Cl ( q) C. Cl ( q) H O & 2 ( l) HCl( q) OH ( q) D.
7/19/2011. Models of Solution Chemistry- III Acids and Bases
Models of Solution Chemistry- III Acids nd Bses Ionic Atmosphere Model : Revisiting Ionic Strength Ionic strength - mesure of totl concentrtion of ions in the solution Chpter 8 1 2 i μ ( ) 2 c i z c concentrtion
1 The Definite Integral As Area
1 The Definite Integrl As Are * The Definite Integrl s n Are: When f () is Positive When f () is positive nd < b: Are under grph of f between nd b = f ()d. Emple 1 Find the re under the grph of y = 3 +
Web Appendix for: Monetary-Fiscal Policy Interactions and Indeterminacy in Post-War U.S. Data. Saroj Bhattarai, Jae Won Lee and Woong Yong Park
We Appendix for: Monetry-Fiscl Policy Interctions nd Indetermincy in Post-Wr U.S. Dt Sroj Bhttri, Je Won Lee nd Woong Yong Prk Jnury 11, 2012 Approximte model Detrend The technology process A t induces
Supplemental Information. Fv-clasp: An Artificially Designed Small Antibody. Fragment with Improved Production
Structure, Volume Supplementl Informtion : An Artificilly Designed Smll Antibody Frgment with Improved Production Comptibility, Stbility, nd Crystllizbility Tko Arimori, Yu Kitgo, Mstk Umitsu, Yuki Fujii,
A. Limits - L Hopital s Rule. x c. x c. f x. g x. x c 0 6 = 1 6. D. -1 E. nonexistent. ln ( x 1 ) 1 x 2 1. ( x 2 1) 2. 2x x 1.
A. Limits - L Hopitl s Rule Wht you re finding: L Hopitl s Rule is used to find limits of the form f ( ) lim where lim f or lim f limg. c g = c limg( ) = c = c = c How to find it: Try nd find limits by
Multicompartment Pharmacokinetic Models. Objectives. Multicompartment Models. 26 July Chapter 30 1
Multicompartment Pharmacokinetic Models Objectives To draw schemes and write differential equations for multicompartment models To recognize and use integrated equations to calculate dosage regimens To
Discrete Mathematics and Probability Theory Spring 2013 Anant Sahai Lecture 17
EECS 70 Discrete Mthemtics nd Proility Theory Spring 2013 Annt Shi Lecture 17 I.I.D. Rndom Vriles Estimting the is of coin Question: We wnt to estimte the proportion p of Democrts in the US popultion,
The missing ingredient in effective-medium theories: Standard deviations USA. University Park, PA 16802, USA
The missing ingredient in effective-medium theories: Stndrd devitions Crig F. Bohren 1,*, Xuerong Xio 2, nd Akhlesh Lkhtki 2 1 Deprtment of Meteorology, Pennsylvni Stte University, University Prk, PA 16802,
Physical-Chemistry Factors Affecting Oral Absorption. Objectives. ph - Partition Theory. 27 September Chapter 23 1
Physical-Chemistry Factors Affecting Oral Absorption Objectives Understand the physical-chemical factors that affect oral absorption Understand the ph-partition hypothesis as it applies to drug absorption
Study on the Calculation of Magnetic Force Based on the Equivalent Magnetic Charge Method
Avilble online t www.sciencedirect.com Physics Procedi 4 () 9 97 Interntionl Conference on Applied Physics nd Industril Engineering Study on the Clcultion of Mgnetic Force Bsed on the Equivlent Mgnetic
( ) where f ( x ) is a. AB/BC Calculus Exam Review Sheet. A. Precalculus Type problems. Find the zeros of f ( x).
AB/ Clculus Exm Review Sheet A. Preclculus Type prolems A1 Find the zeros of f ( x). This is wht you think of doing A2 Find the intersection of f ( x) nd g( x). A3 Show tht f ( x) is even. A4 Show tht
Supplementary Figures.
Supplementry Figures. c c Supplementry Figure 1 13 C NMR spectrum of representtive smple of PCPC in CDCl 3. The polymer ws purified y using DMS/MeH. CH 2 Cl 2 H 2 DMS Supplementry Figure 2 1 H NMR spectrum
AB Calculus Review Sheet
AB Clculus Review Sheet Legend: A Preclculus, B Limits, C Differentil Clculus, D Applictions of Differentil Clculus, E Integrl Clculus, F Applictions of Integrl Clculus, G Prticle Motion nd Rtes This is
Estimation of Global Solar Radiation at Onitsha with Regression Analysis and Artificial Neural Network Models
eserch Journl of ecent Sciences ISSN 77-5 es.j.ecent Sci. Estimtion of Globl Solr dition t Onitsh with egression Anlysis nd Artificil Neurl Network Models Abstrct Agbo G.A., Ibeh G.F. *nd Ekpe J.E. Fculty
CBE 291b - Computation And Optimization For Engineers
The University of Western Ontrio Fculty of Engineering Science Deprtment of Chemicl nd Biochemicl Engineering CBE 9b - Computtion And Optimiztion For Engineers Mtlb Project Introduction Prof. A. Jutn Jn
Week 10: Riemann integral and its properties
Clculus nd Liner Algebr for Biomedicl Engineering Week 10: Riemnn integrl nd its properties H. Führ, Lehrstuhl A für Mthemtik, RWTH Achen, WS 07 Motivtion: Computing flow from flow rtes 1 We observe the
Mixing properties and derived magnitudes of
J. Chem. Thermodynmics 1998, 30, 215 227 Mixing properties nd derived mgnitudes of the system { x1ch 3COOCH 3 x 2CH 3OH ( 1 x x ) CH ( CH ) OH} 1 2 3 2 4 t the temperture 298.15 K A. Rodrıguez, J. Cnos,
Driving Cycle Construction of City Road for Hybrid Bus Based on Markov Process Deng Pan1, a, Fengchun Sun1,b*, Hongwen He1, c, Jiankun Peng1, d
Interntionl Industril Informtics nd Computer Engineering Conference (IIICEC 15) Driving Cycle Construction of City Rod for Hybrid Bus Bsed on Mrkov Process Deng Pn1,, Fengchun Sun1,b*, Hongwen He1, c,
THE RELATIONSHIP BETWEEN PHOSPHATE ABSORPTION AND OXYGEN UPTAKE IN EXCISED BEECH MYCORRHIZAS
New Phytol. (\98\)S8, 67-68\ 67 THE RELATIONSHIP BETWEEN PHOSPHATE ABSORPTION AND OXYGEN UPTAKE IN EXCISED BEECH MYCORRHIZAS BY J. L. HARLEY AND C. C. MCCREADY Deprtments of Forestry nd Botny, South Prks
LECTURE 14. Dr. Teresa D. Golden University of North Texas Department of Chemistry
LECTURE 14 Dr. Teres D. Golden University of North Texs Deprtment of Chemistry Quntittive Methods A. Quntittive Phse Anlysis Qulittive D phses by comprison with stndrd ptterns. Estimte of proportions of
( ) where f ( x ) is a. AB Calculus Exam Review Sheet. A. Precalculus Type problems. Find the zeros of f ( x).
AB Clculus Exm Review Sheet A. Preclculus Type prolems A1 Find the zeros of f ( x). This is wht you think of doing A2 A3 Find the intersection of f ( x) nd g( x). Show tht f ( x) is even. A4 Show tht f
In Vivo Predictive Dissolution Flux Measurements. Konstantin Tsinman, PhD Chief Scientific Officer Pion Inc
In Vivo Predictive Dissolution Flux Measurements Konstantin Tsinman, PhD Chief Scientific Officer Pion Inc ktsinman@pion-inc.com What do we mean by IVIVC? USP 1 : The establishment of a rational relationship
MATH 3795 Lecture 18. Numerical Solution of Ordinary Differential Equations.
MATH 3795 Lecture 18. Numericl Solution of Ordinry Differentil Equtions. Dmitriy Leykekhmn Fll 2008 Gols Introduce ordinry differentil equtions (ODEs) nd initil vlue problems (IVPs). Exmples of IVPs. Existence
( ) as a fraction. Determine location of the highest
AB Clculus Exm Review Sheet - Solutions A. Preclculus Type prolems A1 A2 A3 A4 A5 A6 A7 This is wht you think of doing Find the zeros of f ( x). Set function equl to 0. Fctor or use qudrtic eqution if
The Thermodynamics of Aqueous Electrolyte Solutions
18 The Thermodynmics of Aqueous Electrolyte Solutions As discussed in Chpter 10, when slt is dissolved in wter or in other pproprite solvent, the molecules dissocite into ions. In queous solutions, strong
Unit Six AP Calculus Unit 6 Review Definite Integrals. Name Period Date NON-CALCULATOR SECTION
Unit Six AP Clculus Unit 6 Review Definite Integrls Nme Period Dte NON-CALCULATOR SECTION Voculry: Directions Define ech word nd give n exmple. 1. Definite Integrl. Men Vlue Theorem (for definite integrls)
Probability-Based Seismic Assessments: Implementing Wide-Range Nonlinear Dynamic Analysis Methods
Probbility-Bsed Seismic Assessments: Implementing Nonliner Dynmic Anlysis Methods Ftim Jlyer Postdoctorl Scholr University of Rome L Spienz Cliforni Institute of Technology (CIT) Outline A brief Introduction
Flexible Beam. Objectives
Flexile Bem Ojectives The ojective of this l is to lern out the chllenges posed y resonnces in feedck systems. An intuitive understnding will e gined through the mnul control of flexile em resemling lrge
Homework 04. Acids, Bases, and Salts
HW04 - Acids, Bses, nd Slts! This is preview of the published version of the quiz Strted: Feb 21 t 8:59m Quiz Instruc!ons Homework 04 Acids, Bses, nd Slts Question 1 In the reversible rection HCN + H O
Effect of ph on the Strength and Fatigue of Fused Silica Optical Fiber. A. T. Taylor and M. J. Matthewson
Effect of ph on the Strength nd Ftigue of Fused Silic Opticl Fiber A. T. Tylor nd M. J. Mtthewson EFFECT OF ph ON THE STRENGTH AND FATIGUE OF FUSED SILICA OPTICAL FIBER Andrew T. Tylor, M. John Mtthewson
INVESTIGATION OF A BICYCLO [1.1.1]PENTANE AS A PHENYL REPLACEMENT WITHIN AN LpPLA 2 INHIBITOR
![INVESTIGATION OF A BICYCLO [1.1.1]PENTANE AS A PHENYL REPLACEMENT WITHIN AN LpPLA 2 INHIBITOR](/thumbs/71/65562448.jpg "INVESTIGATION OF A BICYCLO [1.1.1]PENTANE AS A PHENYL REPLACEMENT WITHIN AN LpPLA 2 INHIBITOR")
INVESTIGATION OF A BICYCLO [1.1.1]PENTANE AS A PHENYL REPLACEMENT WITHIN AN LpPLA 2 INHIBITOR Measom, N. D.; Down, K. D.; Hirst, D. J.; Jamieson, C.; Manas, E. S.; Patel, V. K.; and Somers, D. O. Celeste
Computation and Modeling of the Air-Sea Heat and Momentum Fluxes. By Dr. Nasser H. Zaker
Computtion nd Modeling of the Air-e et nd Momentum Fluxes By Dr. Nsser. Zker ICTP June 00 1 Introduction The ocen receives energy through the ir-se interfce by exchnge of momentum nd het. The turbulent
9-1 (a) A weak electrolyte only partially ionizes when dissolved in water. NaHCO 3 is an
Chpter 9 9- ( A ek electrolyte only prtilly ionizes hen dissolved in ter. NC is n exmple of ek electrolyte. (b A Brønsted-ory cid is cule tht dontes proton hen it encounters bse (proton cceptor. By this
A formula sheet and table of physical constants is attached to this paper. Linear graph paper is available.
DEPARTMENT OF PHYSICS AND ASTRONOMY Dt Provided: A formul sheet nd tble of physicl constnts is ttched to this pper. Liner grph pper is vilble. Spring Semester 2015-2016 PHYSICS 1 HOUR Answer questions
PERISTALTIC PUMPING OF A CONDUCTING BINGHAM FLUID IN A CHANNEL
Interntionl Conference on Fluid Dynmics nd Thermodynmics Technologies (FDTT ) IPCSIT vol.33() () IACSIT Press, Singpore PERISTALTIC PUMPING OF A CONDUCTING BINGHAM FLUID IN A CHANNEL S. Venkteswrulu, G.