b ritton c hance department of biochemistry/biophysics icas annual liberty award presentation...
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BRITTON CHANCE
Department of Biochemistry/Biophysics
ICAS Annual Liberty Award Presentation7:30-9:00 PM, December 14, 2005
Science and My LifeScience and My Life
(07/24/1913 ~ )
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My First Invention:My First Invention:Compass Controlled Automatic Ship SteeringCompass Controlled Automatic Ship Steering
Photo Sensor with Negative FeedbackPhoto Sensor with Negative Feedback
(1931-1938)(1931-1938)
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Automatic Ship Steering – Texas SunAutomatic Ship Steering – Texas Sun
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The first optical sensor from magnetic compass The first optical sensor from magnetic compass
Compass
45 o mirror
Prisms
Photocells
(1937)(1937)
US Patents: 2228199, 2228200, 2102511, 2102512, 2102513, 2132676, 2132677, 2182696, 2182717, 2185074, 2289242, 2337589
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The Enzyme-Substrate Compounds The Enzyme-Substrate Compounds and Stopped Flow Apparatusand Stopped Flow Apparatus
Cambridge UniversityCambridge UniversityTrinity CollegeTrinity CollegePhysiology LabPhysiology Lab
(1938-1941)(1938-1941)
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Manually driven syringes
Original Stopped Flow Apparatus made by hand in the Physiological laboratory, Cambridge University FJW Roughton and GA Millikan supervisors of Ph.D. study on enzyme kinetics.
Time range to 0.3 msec and k1 107 M-1sec-1
Lucite mixer made by hand with dental drills
Strings!
Stopped Flow ApparatusStopped Flow Apparatus
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Mechanical Differential Analyzer for Solutions of Non-linear Differential Equations for Enzyme Action
(1936~1937) UPenn Moore School, JG Brainerd
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Computer Fit (Solid Line) to the Experimental Kinetics of Product of Formation fromEnzyme-Substrate Compound (1939)
Computer Fit (Solid Line) to the Experimental Kinetics of Product of Formation fromEnzyme-Substrate Compound (1939)
Product FormationKinetics of Enzyme-
Substrate Compound
620 nm430-405 nm
pkkpexkdt
dp)()( 321 pkpexk
dt
dx21 )(
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The Radar WarThe Radar War (1941-1946) (1941-1946)
MIT Radar Lab Group 63MIT Radar Lab Group 63Precision Timing and Computing CircuitsPrecision Timing and Computing Circuits
SCR-584, SG-3, APA-44, APQ-13, APS-15SCR-584, SG-3, APA-44, APQ-13, APS-15Long Range Navigation (LORAN)Long Range Navigation (LORAN)
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The Radiation Laboratory Steering Committee The Radiation Laboratory Steering Committee ““The Brain Trust” (1943)The Brain Trust” (1943)
Steering committee not shown in the picture: Purcell, Pound, Ramsay, Schwinger, Alvarez and others.
RabiPollard
Bonner
Zacharias Haworth
Herb Marshall
Ridenour
DubridgeEwing
LawsonGetting
LoomisChance
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Elevation Potentiometer
Oil LevelPlug
Oil DrainPlug
Selsyn Compartment
Slip-ring Compartment
Canvas Drain Duct
Elevation Drive Motor
Elevation Gear Housing
Elevation Selsyn Housing
SCR-584SCR-584Radar Lab antiaircraft 10 cm autotracking Radar directly coupled to Bell Labs electronic computer and 5” hydraulically controlled guns.
Action at Anzio, Normandy and Buzzbombs.
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Back to BiochemistryBack to BiochemistryVia Stockholm and Cambridge Via Stockholm and Cambridge
Guggenheim FellowGuggenheim Fellow(with Hugo Theorell and David Keilin)(with Hugo Theorell and David Keilin)
Mitochondrial and Tissue SpectroscopyMitochondrial and Tissue Spectroscopy
(1947-1951) (1947-1951)
Olympic GamesOlympic Games(1952)(1952)
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Training for Helsinki OlympicsTraining for Helsinki Olympics
Sandhamn, SwedenJuly 1952
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Olympic Medal Helsinki 1952Olympic Medal Helsinki 1952
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Gold MedalGold Medal
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BC at Helm of Complex IIIBC at Helm of Complex III
The first USSR world championship, Tallin, Esthonia 1962 First Place
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More Adventures in ScienceMore Adventures in ScienceDual Wavelength SpectroscopyDual Wavelength Spectroscopy
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Time Shared Dual Wavelength Spectrophotometer Time Shared Dual Wavelength Spectrophotometer for Turbid Mitochondrial Suspensionsfor Turbid Mitochondrial Suspensions
MonochromatorSet to A
MonochromatorSet to B
Exit slit
60Hz Vibrating mirror
Half silvered mirror
Sample
Photomultiplier
Light Source
Exit slit
Entrance slit
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Respiration Chain: Respiration Chain: Mitochondria cytochromes flavins and Pyridine nucleotides Reduced minus oxidized spectrumMitochondria cytochromes flavins and Pyridine nucleotides Reduced minus oxidized spectrum
with Ron Williamswith Ron Williams
Keilin’s Cytochromes
Fluorescent NADH and Flavoprotein
NADH Fp Q b c1 c a a3 O2 Oxygen Sensor (10-8M)
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Mitochondrial Function: Fast Response to Energy Demand and Calcium Transport
with Maria Erecinska
Mitochondrial Function: Fast Response to Energy Demand and Calcium Transport
with Maria Erecinska
ADP Ca++
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Intraoperating Flying Spot Scan of mitochondrial flavoprotein fluorescence on exposed Human Brain
STA-MCA Anastomosis (1960)with George Austin
Intraoperating Flying Spot Scan of mitochondrial flavoprotein fluorescence on exposed Human Brain
STA-MCA Anastomosis (1960)with George Austin
BC-X 202
Fp Oxidized
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Quantum Mechanical Electron Tunneling Quantum Mechanical Electron Tunneling in the Photosynthetic Reaction Centerin the Photosynthetic Reaction Center
with Don DeVaultwith Don DeVault(1960-1970)(1960-1970)
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DeVault, D. and Chance, B. (1966) Biophys J 6(6):825-847
General arrangement of the apparatus for photosynthesis with laser pulses. The reactions are followed spectrophotometrically with monochromator photomultiplier and oscilloscope.
Laser Apparatus for Electron Tunnelling Discovery and in Chromatium
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Low Temperature Electron Tunnelling: Cytochrome Oxidation at 77K
Low Temperature Electron Tunnelling: Cytochrome Oxidation at 77K
DeVault, D. and Chance, B. (1966) Biophys J 6(6):825-847
.
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Our Preliminary Tunnelling MechanismOur Preliminary Tunnelling Mechanism
DeVault, D. and Chance, B. (1966) Biophys J 6(6):825-847
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Muscle BioenergeticsMuscle Bioenergetics
MRS of Human LimbsMRS of Human Limbs
(1982 onwards)(1982 onwards)
In Magnet ExerciseIn Magnet Exercisewith Jack Leighwith Jack Leigh
Muscle BioenergeticsMuscle Bioenergetics
MRS of Human LimbsMRS of Human Limbs
(1982 onwards)(1982 onwards)
In Magnet ExerciseIn Magnet Exercisewith Jack Leighwith Jack Leigh
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BC’s Leg in 1.5T MagnetFirst MRS of Human (1982)
BC’s Leg in 1.5T MagnetFirst MRS of Human (1982)
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BC’s head in 13 kilogauss magnet First Head in Magnet (1982)
BC’s head in 13 kilogauss magnet First Head in Magnet (1982)
Model: Mayonnaise
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A New ChapterA New ChapterClinical NIR Imaging: Brain Optical ImagingClinical NIR Imaging: Brain Optical Imaging
(OISO 1996)(OISO 1996)
A New ChapterA New ChapterClinical NIR Imaging: Brain Optical ImagingClinical NIR Imaging: Brain Optical Imaging
(OISO 1996)(OISO 1996)
In order to provide a faster, cheaper, portable brain imager, we turn to NIR spectroscopy and imaging.
Lower resolution but more biochemistry!
With Qingming LuoWith Qingming Luo
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Model for coupling of synaptic activity with glucose utilization.Adapted from Magistretti, P.J., et al (Oct. 1999) NIPS 14: 177-182
At glutamatergic synapses, the action of glutamate is terminated by an efficient glutamate uptake system located in astrocytes (1). Glutamate is cotransported with Na+, resulting in an increase in the intracellular concentration of Na+, leading to the activation of the Na+-K-ATPase (2a). Glutamate is converted to glutamine by glutamine synthase. (2b) Activation of the Na+-K+-ATPase triggers aerobic glycolysis (3). Lactate produced by the glutamate-stimulated glycolysis is released from astrocytes (4). A. synatic activation; B, direct glucose uptake into neurons under basal conditions. Pyr, pyruvate; Lac, lactate; Gln, glutamine; G, G protein; PGK, phosphoglycerate kinase. Copyright (1994) National Academy of Sciences, USA
O2 Utilization
Synaptic JunctionCyanide Sensitive
Astrocyte Cyanide Insensitive
Capillary
Capillary
O2 Glucose
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Arachnoid space
Pia matter (< 1 mm)White matter
Brain cortex(4 mm)
Skull(4-6 mm)
At a fixed separation of sources (4) and detectors (16), the functionally activated signal cause absorption changes according to Beers Law from whcih incremental changes of total hemoglobin (HbT) oxy-deoxy hemoglobin are computed:∆CHbT = ∆OD805 / ∆805 X
L
Where ∆E is the incremental absorption coefficient, ∆OD the absorbance changes in functional activity and L is the photon migration pathlength and saturation of Hb can be computed:
Spectroscopy and Imaging of Human Brain Cortex
HbO2∆Y = HbO2+Hb=
HbO2+Hb1
1+Hb
HbO2
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“oxy” Differential x(850) - y(760)“BV” single ended z(805)
Minimize “oxy” and “BV” crosstalk by adjusting x, y on blood model system
Wavelength Selection Blood -Lipid Model 40 M HbO2
G.A. Millikan (1935) B. Chance (1951)
Dual wavelength measurement of saturation and rejection of blood volume changes
Dual wavelength measurement of saturation and rejection of blood volume changes
BC 368d
JDu 1
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Multi Source Multi Detector NIR ImagerThree Wavelength Time Multiplex 16-Channel NIR Imager
Multi Source Multi Detector NIR ImagerThree Wavelength Time Multiplex 16-Channel NIR Imager
BC 423
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The optical detector of brain function is easily held in place over forehead with Velcro straps
The optical detector of brain function is easily held in place over forehead with Velcro straps
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Cognitive Function: Anagram Solutions
16 Detector NIR Imager
(1996 to date)With S Nioka
NIR PFC Images Brodman's 9&10
Cognitive Function: Anagram Solutions
16 Detector NIR Imager
(1996 to date)With S Nioka
NIR PFC Images Brodman's 9&10
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Display of histograms for 16 pixels in ~700 anagrams solutions
Abscissa: signal strength (blood volume, 1M)Ordinate: number of trials (700)Projected onto the prefrontal cortex Brodman’s 9 & 10.
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Sudden Insight Image NIR “Cognoscope” (EK)
Color representation of mean value of Gaussian fit to histograms
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Are prefrontal “societal inhibitions” Are prefrontal “societal inhibitions” activated in falsehood?activated in falsehood?
Can the deceitful forebrain Can the deceitful forebrain be detected?be detected?
Coll: Drs. Ruben Gur, Dan LanglebenColl: Drs. Ruben Gur, Dan Langleben
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Illustrating oxygenation changes due to false answers to sensitive questions (Subject A)
M=600 tests
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SummarySummary
A pleasant trip through a number of adventures on the road to discovery and competitive achievements in science and sailing.
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Collaborators - University of PennsylvaniaCollaborators - University of Pennsylvania
Shoko NiokaBaruch Ben-DorTao AoPing HuangGwen Lech Zhongyao Zhao Bleu ZhongJun Zhang Juan Du Xiaohong Li Walid M. Fahssi Ulas Sunar Bien Chu Gerald Mullin Chilton Alter
Center for Biomedical Optics Physics Dept.Arjun Yodh
Radiology Dept.J.S. LeighMitchell SchnallJerry Glickson Gang Zheng
Neurology Dept.William Bank
Chemistry Dept.Al GerwitzPonzy Lu
Children’s HospitalTony Simon
Lanlan ZhouCindy Wang Gunay YurtseverSammy ShanYe XingBarry John-Chuan David R. Busch Mahsa RanjiJoohee Im Dan Huang Yingting LiuXiang Cao Hui Sun
NTROIWafik S. El-Deiry
BioengineeringJohn Schotland
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Collaborators - ElsewhereCollaborators - ElsewhereBruce TrombergU.C. Irvine, CA
Nimmi RamanujamUniv. of Wisconsin, Madison, WI
Michael PattersonHamilton, Ontario, Canada
Eva Sevick-MuracaTAMU, College Station, TX
Hanli LiuUniv. of Texas, Arlington, TX
Ken RundellOlympic Center, Lace Placid, NY
Sam AchilefuUniv. of Washington, St. Louis, MO
Maria DelivoriaEnla AndayMedical College of PAPhiladelphia, PA
Ralph Weissleder MGH, Boston, MA
Susan BriestLeipzig, Germany
Kevin McCullyUniv. of GeorgiaAthens, GA
Takafumi HamaokaToyko, Japan
H. KoizumiHitachi, Tokyo, Japan
Maria Anglina FranchesciniMGH, Boston, MA
Christopher H. ContagNTROI, Stanford
Ching H. Tung MGH, Boston, MA