1. Universal laws and architectures: Theory and lessons from nets, grids, brains, bugs, planes, docs, fire, fashion, art, turbulence, music, buildings, cities, earthquakes, bodies, running, throwing, Synesthesia, spacecraft, statistical mechanics slow inflexible fragile waste

2. eye vision Act delay Control noise error P + noise error C Understand this more deeply? + Neuroscience Mechanics+ Gravity + Light + Control theory

3. eye vision Act delay Control noise error Understand this more deeply? + Neuroscience Vision Motion

4. Robust vision w/motion Object motion Self motion Vision Motion eye vision Act delay Control noise error

5. Fast Slow Flexible Inflexible Vision Explain this amazing system. Layering Feedback

6. Experiment Motion/vision control without blurring Which is easier and faster? Robust vision with Hand motion Head motion

7. Fast Slow VOR vision Why? Mechanism Tradeoff Cerebellum

8. Fast Slow Flexible Inflexible VOR vision Vestibular Ocular Reflex (VOR) Mechanism Tradeoff

9. Slow Flexible vision eye vision Act slow delay Fast Inflexible

10. Slow Flexible vision eye vision Act slow delay Fast Inflexible VOR fast

11. Slow Flexible eye Act Fast Inflexible VOR fast Vestibular Ocular Reflex (VOR)

12. Slow Flexible eye Act Fast Inflexible VOR fast It works in the dark or with your eyes closed, but you can’t tell.

13. Slow Flexible vision eye vision Act slow delay Fast Inflexible VOR fast

14. vision eye vision Act slow delay VOR Slow Flexible Fast Inflexible Illusion Highly evolved (hidden) architecture Layering Feedback

15. eye vision Act VOR Layering Automatic Unconscious Partially Conscious Cerebellum

16. eye vision Act slow delay VOR fast Layering Feedback

17. vision eye vision Act slow delay VOR Slow Flexible Fast Inflexible Illusion fast Architecture layered/ distributed

18. vision eye vision Act slow delay VOR Slow Flexible Fast Inflexible Illusion fast Architecture layered/ distributed Robust or fine-tuned? Both Modular or plastic? Both

19. Cortex eye vision Act slow delay VOR fast Object motion Head motion Error + Very rough cartoon

20. Cortex eye vision Act slow delay VOR fast Object motion Head motion Cerebellum Error + Tune gain Slightly better gain AOS AOS = Accessory Optical system

21. Cortex eye vision Act slow delay VOR This fast “forward” path Object motion Head motion Cerebellum Error + Tune gain Slightly better gain AOS AOS = Accessory Optical system Needs “feedback” tuning Via AOS and cerebellum (not cortex)

22. Cortex eye vision Act slow delay VOR fast Object motion Head motion Cerebellum + Error Tune gain gain AOS AOS = Accessory Optical system noise Act Highly evolved (hidden) architecture

23. Cortex eye vision Act slow delay VOR fast Object motion Head motion Cerebellum + Error Tune gain gain AOS AOS = Accessory Optical system noise Act slowest

24. Cortex eye vision Act slow delay VOR fast Object motion Head motion Cerebellum + Error Tune gain gain AOS AOS = Accessory Optical system noise Act Delays everywhere Distributed control slowest

25. Cortex eye vision Act slow delay VOR fast Object motion Head motion Cerebellum + Error Tune gain gain AOS noise Act slowest Heterogeneous delays everywhere

26. Slow Flexible vision eye vision Act slow delay Fast Inflexible VOR fast 3D + motion See Marge Livingstone Color?Color?

27. Slow Flexible vision eye vision Act slow delay Fast Inflexible VOR fast See Marge Livingstone 3D + motion color vision SlowestSlowest

28. Stare at the intersection

30. Stare at the intersection.

36. Slow Flexible vision eye vision Act slow delay Fast Inflexible VOR fast 3D + motion color vision SlowestSlowest

37. Slow Flexible vision Fast Inflexible VOR color vision Seeing is dreaming is simulation requiring “internal model ”

38. gradient Biased random walk Ligand Signal Transduction MotionMotor CheY

39. Bacterial chemotaxis Internal model necessary for robust chemotaxis Reality is 3d, but… Internal model virtual and 1d

40. Slow Flexible vision Fast Inflexible VOR color vision Layering Distributed Feedback

41. Slow Flexible Fast Inflexible Impossible (law) Architecture Architecture (constraints that deconstrain) General Special Universal laws and architectures (Turing) ideal

42. Slow Flexible Fast Inflexible General Special NP(time) P(time) analytic Npspace=Pspace Decidable Computation (on and off-line)

43. Slow Flexible Fast Inflexible NP P analytic Pspace Decidable Insight Research progress Control, OR Compute From toys to “real” systems

44. Slow Flexible Fast Inflexible NP P analytic Pspace Decidable Insight Research progress Control, OR Compute Improved algorithms

45. Slow Flexible vision Fast Inflexible VOR color vision Layering Distributed Feedback

46. Cortex eye vision Act slow delay VOR This fast “forward” path Object motion Head motion Cerebellum Error + Tune gain Slightly better gain AOS AOS = Accessory Optical system Needs “feedback” tuning Via AOS and cerebellum (not cortex)

47. Cortex eye vision Act slow delay VOR fast Object motion Head motion Cerebellum + Error Tune gain gain AOS AOS = Accessory Optical system noise Act

48.    Real (NP hard) Complex = LTI (??) Operator valued or Noncomm (P) Scale with dimension? Uncertainty everywhere

49. vision eye vision Act slow delay VOR Slow Flexible Fast Inflexible Illusion Highly evolved (hidden) architecture Layering Distributed Feedback

50. eye vision delay .3s Act delay Control noise error

51. Model? 1 dimension, 4 states? Other 2 dimensions? New issues arise

52. eye vision Act delay Control noise error

53. eye vision Act delay Control noise error easy hard

54. eye vision Act delay Control noise error easy hard

55. eye vision Act delay Control noise error Close one eye?

56. 10 100 Length, m.11.5.2 2 10 10 0 1 0 1 too fragile complex No tradeoff expensive fragile Slow Flexible vision eye vision Act slow delay Fast Inflexible VOR fast Universal laws?

57. 10 100 Length, m.11.5.2 2 Slow Flexible vision eye vision Act slow delay Fast Inflexible VOR fast How do these fit together?

58. slow flexible fast inflexible How do these fit together? “waste”“efficient” fragile robust vision VOR delay

59. sec/m.01 1.1 area.1110 diam(  m).011100 Retinal ganglion axons? Other myelinated Why such extreme diversity in axon size and delay?

60. .01 1 delay sec/m AαAα C.1 AβAβ Aγ AδAδ area.1110 diam(  m).011100 Axon size and speed Fast Small Slow Large

61. delay sec/m.01 1.1 area.1110 diam(  m).011100 Retinal ganglion axons? Other myelinated Why such extreme diversity in axon size and delay? VOR No diversity in VOR? Resolution and bandwidth are cheap speed costs

62. axon Same area = same “cost” axon 2 x resolution (less noise) axon Double the area (and cost)? speed costs Resolution and bandwidth are cheap

63. vision Act delay 10 100 Speed  1/ .11.5.2 2 Slower axon 2 x resolution (less noise) axon speed doubly expensive but necessary

64. Cortex eye vision Act slow delay VOR fast Object motion Head motion Cerebellum + Error Tune gain gain AOS AOS = Accessory Optical system noise Act Delays everywhere Distributed control slowest

65. Cortex eye vision Act slow delay VOR fast Object motion Head motion Cerebellum + Error Tune gain gain AOS noise Act slowest Heterogeneous delays everywhere

66. Fast Slow Flexible Inflexible Reflex SenseMotor Prefrontal Fast Learn Evolve Apps OS HW vision Act delay axon 2 x resolution (less noise) axon speed doubly expensive but necessary

67. slow flexible fast inflexible How do these fit together? “waste”“efficient” fragile robust vision VOR delay speed costs

68. slow flexible fast inflexible In general? wastefulefficient fragile robust

69. slow flexible fast inflexible fragile robust wasteefficient fragile robust

70. slow flexible fast inflexible fragile robust waste efficient fragile robust Cyber-physical Cyber only

71. slow flexible fast inflexible waste efficient fragile robust Cyber-physical

72. accessible accountable accurate adaptable administrable affordable auditable autonomy available compatible composable configurable correctness customizable debugable degradable determinable demonstrable dependable deployable discoverable distributable durable effective evolvable extensible fail transparent fast fault-tolerant fidelity flexible inspectable installable Integrity interchangeabl e interoperable learnable maintainable manageable mobile modifiable modular nomadic operable orthogonalit y portable precision predictable producible provable recoverable relevant reliable repeatable reproducible resilient responsive reusable safety scalable seamless self-sustainable serviceable supportable securable simple stable standards survivable tailorable testable timely traceable ubiquitous understandable upgradable usable efficient robust sustainable PCA  Principal Concept Analysis flexible fast efficient robust

73. slow flexible fast inflexible waste efficient

74. slow flexible fast inflexible waste efficient Slow Inflexible Fragile Waste slow inflexible fragile waste Same picture

75. Control, OR Communicate Compute Physics Shannon Bode Turing Gödel Einstein Heisenberg Carnot Boltzmann Theory? Deep, but fragmented, incoherent, incomplete Nash Von Neumann

76. Priorities Functionality (behavior, semantics) Robustness –Uncertain environment and components –Fast (sense, decide, act) –Flexible (adaptable, evolvable) Efficiency –Energy –Other resources (make and maintain)

77. Control, OR Compute Functionality (behavior, semantics) Robustness –Uncertain environment and components –Fast (sense, decide, act) –Flexible (adaptable, evolvable) Efficiency –Energy –Other resources (make and maintain) Function, delay, robustness most important

78. Functionality (behavior, semantics) Robustness – Uncertain environment and components – Fast (sense, decide, act) – Flexible (adaptable, evolvable) Efficiency – Energy – Other resources (make and maintain) Communicate Physics Info theory

79. Functionality (behavior, semantics) Robustness – Uncertain environment and components – Fast (sense, decide, act) – Flexible (adaptable, evolvable) Efficiency – Energy – Other resources (make and maintain) Communicate Physics Info theory Noise, average, asymptotic

80. Control, OR Info theoryCompute Physics Function, delay, robustness most important Function, delay, robustness least important

81. Control, OR Info theoryCompute Physics Shannon Bode Turing Einstein Heisenberg Carnot Boltzmann Function, delay, robustness most important Function, delay, robustness least important Dominates “high impact science” literature

82. Slow Flexible Fast Inflexible NP P analytic Pspace Decidable Insight Research progress Control, OR Compute From toys to “real” systems

83. Slow Flexible Fast Inflexible NP P analytic Pspace Decidable Insight Research progress Control, OR Compute Improved algorithms

84. Control, OR Info theoryCompute Physics Shannon Bode Turing Einstein Heisenberg Carnot Boltzmann Function, delay, robustness most important Function, delay, robustness least important

85. Function, delay, robustness most important Function, delay, robustness least important Control, OR CommunicateCompute Physics Shannon Bode Turing New progress!

86. Control, OR Compute Physics Bode Turing New progress! Coherent structures and turbulent drag Function, delay, robustness least important

87. Shear flow turbulence Exhaustively studied – Extensive experiments and big data – Detailed models and big simulations – Great! But all just deepen the mystery Perfectly illustrates robust/fragile Without which? Bewilderment. Physics of Fluids (2011)

88. z x y z x y Flow upflow high-speed region downflow low speed streak Blunted turbulent velocity profile Laminar Turbulent 3D coupling Coherent structures and turbulent drag

89. wasteful fragile Laminar Turbulent efficient robust Laminar Turbulent ? Control? Fundamentals!

90. Control, OR Compute Bode Turing New progress! Communications for control, computing, biology Function, delay, robustness least important

91. Internal delays SenseMotor Prefrontal Fast Learn Reflex Evolve vision VOR Communications for control, computing, biology

92. Internal delays New theory: Distributed control with delays everywhere. Sense/Act Compute/communicate Physical

93. Info Thry Control, OR Compute Physics Orthophysics (Eng/Bio/Math) Optimization Statistics Comms for Comp/Cntrl/Bio Theory

94. wasteful fragile Laminar Turbulent efficient robust ? Control? Info Thry Physics Orthophysics (Eng/Bio/Math) Laminar Turbulent z x y Flow

95. Doyle, Csete, Proc Nat Acad Sci USA, JULY 25 2011 For more info Most accessible No math References

96. wasteful fragile efficient robust Impossible (law) Architecture Universal laws and architectures Flexibly achieves what’s possible

97. Efficiency/instability/layers/feedback Sustainable infrastructure? (e.g. smartgrids) Money/finance/lobbyists/etc Industrialization Society/agriculture/weapons/etc Bipedalism Maternal care Warm blood Flight Mitochondria Oxygen Translation (ribosomes) Glycolysis (2011 Science) Major transitions Evolvability?

98. control feedback RNA mRNA RNAp Transcription Other Control Gene Amino Acids Proteins Ribosomes Other Control Translation Metabolism Products Signal transduction ATP DNA New gene SensoryMotor Prefrontal Striatum Reflex Learning Software Hardware Digital Analog Horizontal Gene Transfer Horizontal App Transfer Horizontal Meme Transfer Accelerating evolution Requires shared “OS”

99. Horizontal Gene Transfer Sequence ~100 E Coli (not chosen randomly) ~ 4K genes per cell ~20K different genes in total (pangenome) ~ 1K universally shared genes ~ 300 essential (minimal) genes

100. control feedback RNA mRNA RNAp Transcription Other Control Gene Amino Acids Proteins Ribosomes Other Control Translation Metabolism Products Signal transduction ATP DNA New gene SensoryMotor Prefrontal Striatum Reflex Learning Software Hardware Digital Analog Horizontal Gene Transfer Horizontal App Transfer Horizontal Meme Transfer What can go wrong?

101. Horizontal Bad Gene Transfer Horizontal Bad App Transfer Horizontal Bad Meme Transfer Parasites & Hijacking Fragility? Exploiting layered architecture Virus Meme

102. Horizontal Bad Meme Transfer Our greatest fragility? Meme Many human beliefs are: False Unhealthy

103. Slow Flexible vision Fast Inflexible VOR

104. Slow Flexible vision eye vision Act slow delay Fast Inflexible VOR fast

105. Cortex eye vision Act slow delay VOR fast Object motion Head motion Cerebellum + Error Tune gain gain AOS AOS = Accessory Optical system noise Act Delays everywhere Distributed control slowest

106. Slow Flexible vision eye vision Act slow delay Fast Inflexible VOR fast

107. Vision - slow VOR fast Fast Slow Flexible Inflexible slower Mixed Redraw (not anatomical)

108. Vision - 3d+motion B&W slow VOR fast Fast Slow Flexible Inflexible slower Objects Mixed Redraw (not anatomical)

109. 3d+motion B&W slow Fast Slow Flexible Inflexible slower Objects

111. - 3d+motion B&W slow VOR fast Fast Slow Flexible Inflexible Faces slower Objects Mixed Not sure how to draw this…

112. Chess experts can reconstruct entire chessboard with < ~ 5s inspection can recognize 1e5 distinct patterns can play multiple games blindfolded and simultaneous are no better on random boards (Simon and Gilmartin, de Groot) www.psywww.com/intropsych/ch07_cognition/expertise_and_domain_specific_knowledge.html

113. Specific brain lesions can cause “blindness” to Faces Fruit or Animals or Tools or ?? Left side of body Movement Nonmovement ???

114. Fast Slow Flexible Inflexible Faces slower Objects Not sure how to draw this… Learning +evolution

115. When needed, even wasps can do it.

116. Polistes fuscatus can differentiate among normal wasp face images more rapidly and accurately than nonface images or manipulated faces. Polistes metricus is a close relative lacking facial recognition and specialized face learning. Similar specializations for face learning are found in primates and other mammals, although P. fuscatus represents an independent evolution of specialization. Convergence toward face specialization in distant taxa as well as divergence among closely related taxa with different recognition behavior suggests that specialized cognition is surprisingly labile and may be adaptively shaped by species-specific selective pressures such as face recognition.

117. Fig. 1 Images used for training wasps. M J Sheehan, E A Tibbetts Science 2011;334:1272-1275 Published by AAAS

118. vision eye vision Act slow delay VOR Slow Flexible Fast Inflexible Illusion Highly evolved (hidden) architecture Seeing is dreaming

119. - 3d+motion B&W slow VOR fast Fast Slow Flexible Inflexible Faces slower Objects Mixed Not sure how to draw this… Learning +evolution

120. Sense Universal tradeoffs? Fast Slow Flexible Inflexible Motor Prefrontal Fast Learn Reflex Evolve Learning can be very slow. Evolution is even slower. Cerebellum

121. control feedback RNA mRNA RNAp Transcription Other Control Gene Amino Acids Proteins Ribosomes Other Control Translation Metabolism Products Signal transduction ATP DNA New gene SensoryMotor Prefrontal Striatum Reflex Learning Software Hardware Digital Analog Horizontal Gene Transfer Horizontal App Transfer Horizontal Meme Transfer Accelerating evolution Requires shared “OS”

122. control feedback RNA mRNA RNAp Transcription Other Control Gene Amino Acids Proteins Ribosomes Other Control Translation Metabolism Products Signal transduction ATP DNA New gene SensoryMotor Prefrontal Striatum Reflex Learning Software Hardware Digital Analog Gene Transfer App Transfer Meme Transfer Some genes, apps, ideas are “invented” But most bacteria and people get most of them from others

123. costly fragile efficient robust Learning

124. crawl walk bike Learning

125. Cortex eye vision Act slow delay VOR fast Object motion Head motion Cerebellum + Error Tune gain gain AOS AOS = Accessory Optical system noise Act

126. Cortex eye vision Act slow delay VOR fast Object motion Head motion Cerebellum + Error Tune gain gain AOS AOS = Accessory Optical system noise Act Reflex

127. SensoryMotor Prefrontal Striatum Slow Flexible Slow Flexible Learning Ashby & Crossley Slow Reflex (Fastest, Least Flexible) Extreme heterogeneity

128. SensoryMotor Prefrontal Striatum Fast Inflexible Fast Inflexible Slow Flexible Slow Flexible Learning Reflex (Fastest, Least Flexible) Ashby & Crossley Learning can be very slow.

129. Sense Fast Slow Flexible Inflexible Motor Prefrontal Fast Learn Reflex Evolve HMT Teach Horizontal Meme Transfer

130. Sense Fast Slow Flexible Inflexible Motor Prefrontal Fast Learn Reflex Evolve Horizontal Hardware Transfer HHT

131. Sense Fast Slow Flexible Inflexible Motor Prefrontal Fast Learn Reflex Evolve Apps OS HW HMT HHT

132. Sense Fast Slow Flexible Inflexible Motor Prefrontal Fast Learn Reflex Evolve HMT Soma Reactive Adaptive Contextual Cerebellum

133. Sense Fast Slow Flexible Inflexible Motor Prefrontal Fast Learn Reflex Evolve Apps OS HW

134. Fast Costly Slow Cheap Flexible Inflexible General Special Layered Architecture Apps OS HW Digital Lumped Distrib. OS HW Digital Lumped Distrib. Digital Lumped Distrib. Lumped Distrib. Any layer needs all lower layers.

135. Fast Slow Flexible Inflexible Apps OS HW Apps OS Hardware Digital Lumped Distributed Tech implications/extensions

136. Slow Flexible Fast Inflexible Impossible (law) Architecture Architecture (constraints that deconstrain) General Special Universal laws and architectures (Turing) ideal

137. Slow Flexible Fast Inflexible General Special NP(time) P(time) analytic Npspace=Pspace Decidable Computation (on and off-line)

138. Slow Flexible Fast Inflexible General Special NP P analytic Pspace Decidable Computation (on and off-line) Insight Accessible Verifiable

139. Slow Flexible Fast Inflexible NP P analytic Pspace Decidable Insight Research progress Control, OR Compute From toys to “real” systems

140. Slow Flexible Fast Inflexible NP P analytic Pspace Decidable Insight Research progress Control, OR Compute Improved algorithms

141. P(time) (delay) Pspace (memory, bandwidth) Resource cost vs effectiveness CheapCostly Strong Weak To make In use Talk Energy

142. Pspace (memory, bandwidth) Cheap Strong To make In use 1 TB < $100 $50 $?? 1 TB = 1e12B

143. P(time) Pspace (memory, bandwidth) What dominates tradeoffs CheapCostly Strong Weak To make In use Talk Energy

144. time What dominates tradeoffs CostlyCheap Fast Slow Energy

145. time What dominates tradeoffs CostlyCheap Fast Slow Energy Flexible Inflexible

146. time What dominates tradeoffs Fast Slow Flexible Inflexible

147. Slow Flexible Fast Inflexible General Special NP(time) P(time) analytic Pspace Decidable Computation (on and off-line)

148. Slow Flexible Fast Inflexible General Special NP(time) P(time) analytic Pspace Decidable Universal architecture Universal TM

149. 10 100 Length, m.11.5.2 2 10 10 0 1 0 1 too fragile complex No tradeoff expensive fragile Slow Flexible vision eye vision Act slow delay Fast Inflexible VOR fast Slow Flexible Fast Inflexible General Special NP P analytic Pspace Decidable

150. control feedback RNA mRNA RNAp Transcription Other Control Gene Amino Acids Proteins Ribosomes Other Control Translation Metabolism Products Signal transduction ATP DNA New gene SensoryMotor Prefrontal Striatum Reflex Learning Software Hardware Digital Analog Horizontal Gene Transfer Horizontal App Transfer Horizontal Meme Transfer Accelerating evolution Requires shared “OS”

151. Sense Fast Slow Flexible Inflexible Motor Prefrontal Fast Learn Reflex Evolve Apps OS HW HMT

152. Fast Slow Flexible Inflexible General Special Apps OS HW Exploiting layered architecture

153. Core protocols OS seems to confuse Replace with “core protocols”? Examples different than OS or translation: –Core metabolism –2 component signal transduction Highly conserved/constrained core (knot) Highly diverse/deconstrained edges 153

154. slow flexible fast inflexible waste efficient fragile robust

155. slow flexible fast inflexible waste efficient body brain Combo

156. Sense Fast Slow Flexible Inflexible Motor Prefrontal Fast Learn Reflex Evolve HMT Soma Reactive Adaptive Contextual Cerebellum Combo

157. Slow Fast Flexible Inflexible General Special Apps OS HW Dig. Lump. Distrib. OS HW Dig. Lump. Distrib. Digital Lump. Distrib. Lumped Distrib. HGT DNA repair Mutation DNA replication Transcription Translation Metabolism Signal SenseMotor Prefrontal Fast Learn Reflex Evolve vision VOR

158. Slow Fast Flexible Inflexible General Special Apps OS HW Dig. Lump. Distrib. OS HW Dig. Lump. Distrib. Digital Lump. Distrib. Lumped Distrib. Apps OS HW

159. Fast Slow Flexible Inflexible General Special Apps OS HW Horizontal App Transfer Horizontal Hardware Transfer

160. Fast Slow Flexible Inflexible General Special Apps OS HW

161. OS Horizontal App Transfer Horizontal Hardware Transfer Constrained Deconstrained

162. Horizontal Transfer Constrained Deconstrained

163. Constrained Deconstrained

164. food Glucose Oxygen Organs Tissues Cells Molecules Universal metabolic system Blood Efficient Robust Evolvable

165. food Glucose Oxygen Organs Tissues Cells Molecules Blood Efficient Robust Evolvable Constrained Deconstrained

166. Efficient Robust Evolvable Constrained Deconstrained Diverse

167. Efficient Robust Evolvable Constrained Deconstrained Diverse OS Deconstrained (Hardware) Deconstrained (Applications) Constrained universal architectures

168. Fast Slow Flexible Inflexible General Special Apps OS HW Horizontal App Transfer Horizontal Hardware Transfer

169. Fast Costly Slow Cheap Flexible Inflexible HGT DNA repair Mutation DNA replication Transcription Translation Metabolism Signal… Layered Architecture control feedback RNA mRNA RNAp Transcription Other Control Gene Amino Acids Proteins Ribosomes Other Control Translation Metabolism Products Signal transduction ATP DNA New gene

170. Fast Costly Slow Cheap Flexible Inflexible HGT DNA repair Mutation DNA replication Transcription Translation Metabolism Signal… Layered Architecture RNA mRNA RNAp Transcription Gene Amino Acids Proteins Ribosomes Translation Metabolism Products Core Protocols

171. Fast Costly Slow Cheap Flexible control feedback RNA mRNA RNAp Transcription Other Control Gene Amino Acids Proteins Ribosomes Other Control Translation Metabolism Products Signal transduction ATP DNA New gene Metabolism

172. Fast Costly Slow Cheap Flexible control feedback RNA mRNA RNAp Transcription Other Control Gene Amino Acids Proteins Ribosomes Other Control Translation Metabolism Products Signal transduction ATP DNA New gene Metabolism

173. Fast Costly Slow Cheap Flexible control feedback RNA mRNA RNAp Transcription Other Control Gene Amino Acids Proteins Ribosomes Other Control Translation Metabolism Products Signal transduction ATP DNA New gene Signal Transduction

174. Fast Costly Slow Cheap Flexible control feedback RNA mRNA RNAp Transcription Other Control Gene Amino Acids Proteins Ribosomes Other Control Translation Metabolism Products Signal transduction ATP DNA New gene Signal Transduction

175. TransmitterReceiver Variety of Ligands & Receptors Variety of responses TransmitterReceiver Variety of Ligands & Receptors Variety of responses TransmitterReceiver Variety of Ligands & Receptors Variety of responses TransmitterReceiver Variety of Ligands & Receptors Variety of responses TransmitterReceiver Variety of Ligands & Receptors Variety of responses TransmitterReceiver Variety of Ligands & Receptors Variety of responses TransmitterReceiver Variety of Ligands & Receptors Variety of responses TransmitterReceiver Variety of Ligands & Receptors Variety of responses TransmitterReceiver Variety of Ligands & Receptors Variety of responses TransmitterReceiver Variety of Ligands & Receptors Variety of responses TransmitterReceiver Variety of Ligands & Receptors Variety of responses TransmitterReceiver Variety of Ligands & Receptors Variety of responses TransmitterReceiver Variety of Ligands & Receptors Variety of responses  50 such “two component” systems in E. Coli All use the same protocol - Histidine autokinase transmitter - Aspartyl phospho-acceptor receiver Huge variety of receptors and responses Also multistage (phosphorelay) versions Signal transduction

176. TransmitterReceiver Ligands & Receptors Responses Shared protocols Flow of “signal” Recognition, specificity “Name resolution” within signal transduction Transmitter must locate “cognate” receiver and avoid non-cognate receivers Global search by rapid, local diffusion Limited to very small volumes

177. TransmitterReceiver Ligands & Receptors Responses TransmitterReceiver Ligands & Receptors Responses TransmitterReceiver Ligands & Receptors Responses Shared protocols Flow of “signal” Recognition, specificity

178. Variety of Ligands & Receptors Variety of responses Variety of Ligands & Receptors Variety of Ligands & Receptors Variety of Ligands & Receptors Variety of Ligands & Receptors Variety of Ligands & Receptors Variety of responses Variety of Ligands & Receptors Variety of responses Variety of Ligands & Receptors Variety of responses Variety of Ligands & Receptors Variety of responses Variety of Ligands & Receptors Variety of responses Variety of Ligands & Receptors Variety of responses Variety of Ligands & Receptors Variety of responses Variety of Ligands & Receptors Variety of responses Huge variety Huge variety TransmitterReceiver TransmitterReceiver TransmitterReceiver Recognition, specificity Huge variety Combinatorial Almost digital Easily reprogrammed Located by diffusion

179. TransmitterReceiver TransmitterReceiver TransmitterReceiver Flow of “signal” Limited variety Fast, analog (via #) Hard to change Reusable in different pathways

180. Internet sites Users TransmitterReceiver Ligands & Receptors Responses Shared protocols Flow of “signal” Recognition, specificity Note: Any wireless system and the Internet to which it is connected work the same way. LaptopRouter Flow of packets Recognition, Specificity (MAC)

181. Fast Costly Slow Cheap Flexible Inflexible HGT DNA repair Mutation DNA replication Transcription Translation Metabolism Signaling Layered Architecture control feedback RNA mRNA RNAp Transcription Other Control Gene Amino Acids Proteins Ribosomes Other Control Translation Metabolism Products Signal transduction ATP DNA New gene

182. gradient Biased random walk Ligand Signal Transduction MotionMotor CheY

183. More necessity and robustness Integral feedback and signal transduction (bacterial chemotaxis, G protein) (Yi, Huang, Simon) Example of “exploratory process”

184. Random walk Ligand MotionMotor Bacterial chemotaxis

185. gradient Biased random walk Ligand Signal Transduction MotionMotor CheY

186. Ligand Signal Transduction MotionMotor CheY

187. Ligand Signal Transduction MotionMotor CheY Component of feedback controller

188. Ligand MotionMotor CheY TransmitterReceiver Receptor Response Component of feedback controller

189. PMF + + + + From Taylor, Zhulin, Johnson Variety of receptors/ ligands Common cytoplasmic domains Common signal carrier Common energy carrier

190. Transmitter Receiver Motor Variety of receptors & ligands

191. Ligand MotionMotor CheY Transmitter Receiver Motor Variety of receptors & ligands

193. CheY TransmitterReceiver Receptor Response Integral feedback internal to signaling network

194. Ligand Motion Motor CheY TransmitterReceiver Receptor Response Integral feedback internal to signaling network Main feedback control loop

195. Ligand Signal Transduction MotionMotor CheY

196. gradient Biased random walk Ligand Signal Transduction MotionMotor CheY

198. Tumbling bias Signal Transduction Motor Perfect adaptation is necessary … ligand

199. Tumbling bias ligand Perfect adaptation is necessary … …to keep CheYp in the responsive range of the motor.

200. Tumbling bias

201. Ligand F + F   ln(S)   Integral feedback

202. TransmitterReceiver Variety of Ligands & Receptors Response

203. Diverse Deconstrained (Hardware) Deconstrained (Applications) Diverse Layered architectures Constrained But hidden Apps OS HW Core Protocols Cerebellum

204. ? Deconstrained (Hardware) Deconstrained (Applications) Next layered architectures (SDN) Constrained Optimize & control, share, virtualize, manage resources Comms Memory, storage Latency Processing Cyber-physical Few global variables Don’t cross layers

205. The essence of layering Physical resources Optimize & control, share, virtualize, manage resources Applications 

206. The essence of networking Physical Control Apps Control Physical Apps Control Physical Apps Virtual

207. Prosen- cephalon Telen- cephalon Rhinencephalon, Amygdala, Hippocampus, Neocortex, Basal ganglia, Lateral ventricles Dien- cephalon Epithalamus, Thalamus, Hypothalamus, Subthalamus, Pituitary gland, Pineal gland, Third ventricle Brain stem Mesen- cephalon Tectum, Cerebral peduncle, Pretectum, Mesencephalic duct Rhomb- encephalon Meten- cephalon Pons, Cerebellum Myelen- cephalon Medulla oblongata Spinal cord CNS HW “stack” ? Diverse? Deconstrained (Hardware) Deconstrained? (Applications) Diverse Layered architectures?? Constrained Brain

208. Fast Slow Flexible Inflexible General Special Apps OS HW Horizontal App Transfer Horizontal Hardware Transfer

209. Fast Costly Slow Cheap Flexible Inflexible General Special Layered Architecture Apps OS HW Digital Lumped Distrib. OS HW Digital Lumped Distrib. Digital Lumped Distrib. Lumped Distrib. Any layer needs all lower layers.

210. 0.HGT 1.DNA repair 2.Mutation 3.DNA replication 4.Transcription 5.Translation 6.Metabolism 7.Signal transduction 8.… Apps OS Hardware Digital Lumped Distributed Any layer needs all lower layers. control feedback RNA mRNA RNAp Transcription Other Control Gene Amino Acids Proteins Ribosomes Other Control Translation Metabolism Products Signal transduction ATP DNA New gene

211. Horizontal Gene Transfer Sequence ~100 E Coli (not chosen randomly) ~ 4K genes per cell ~20K different genes in total (pangenome) ~ 1K universally shared genes ~ 300 essential (minimal) genes

212. control feedback RNA mRNA RNAp Transcription Other Control Gene Amino Acids Proteins Ribosomes Other Control Translation Metabolism Products Signal transduction ATP DNA New gene Fast Costly Slow Cheap Flexible Inflexible General Special HGT DNA repair Mutation DNA replication Transcription Translation Metabolism Signal… Layered Architecture

213. Slow Fast Flexible Inflexible General Special Apps OS HW Dig. Lump. Distrib. OS HW Dig. Lump. Distrib. Digital Lump. Distrib. Lumped Distrib. HGT DNA repair Mutation DNA replication Transcription Translation Metabolism Signal SenseMotor Prefrontal Fast Learn Reflex Evolve vision VOR

214. Slow Fast Flexible Inflexible General Special Apps OS HW Dig. Lump. Distrib. OS HW Dig. Lump. Distrib. Digital Lump. Distrib. Lumped Distrib. HGT DNA repair Mutation DNA replication Transcription Translation Metabolism Signal SenseMotor Prefrontal Fast Learn Reflex Evolve VOR Many systems/organisms only use lower layers

215. Lumped Distrib. Metabolism Signal SenseMotor Fast Reflex Evolve VOR Many systems/organisms only use lower layers Analog Red blood cells Normocephalic anucleosis Most metazoans

216. SenseMotor Fast Reflex Evolve Analog? Most metazoans

217. Lumped Distrib. Metabolism Signal SenseMotor Fast Reflex Evolve Many systems/organisms only use lower layers Analog Red blood cells Normocephalic anucleosis Most metazoans

218. 200 microns Denucleated neurons Megaphragma mymaripenne 5 day lifespan 7,400 neurons vs housefly 340,000 honeybee 850,000. Normocephalic anucleosis

219. Slow Fast Flexible Inflexible General Special Apps OS HW Dig. Lump. Distrib. OS HW Dig. Lump. Distrib. Digital Lump. Distrib. Lumped Distrib. HGT DNA repair Mutation DNA replication Transcription Translation Metabolism Signal SenseMotor Prefrontal Fast Learn Reflex Evolve vision VOR

220. 10 100 Length, m.11.5.2 2 10 10 0 1 0 1 too fragile complex No tradeoff expensive fragile Slow Flexible vision eye vision Act slow delay Fast Inflexible VOR fast Slow Flexible Fast Inflexible General Special NP P analytic Pspace Decidable

221. control feedback RNA mRNA RNAp Transcription Other Control Gene Amino Acids Proteins Ribosomes Other Control Translation Metabolism Products Signal transduction ATP DNA New gene SensoryMotor Prefrontal Striatum Reflex Learning Software Hardware Digital Analog Horizontal Gene Transfer Horizontal App Transfer Horizontal Meme Transfer What can go wrong? Before exploring mechanisms

222. Horizontal Bad Gene Transfer Horizontal Bad App Transfer Horizontal Bad Meme Transfer Parasites & Hijacking Fragility? Exploiting layered architecture Virus Meme

223. Horizontal Bad Meme Transfer Our greatest fragility? Meme Many human beliefs are: False Unhealthy

224. Horizontal Bad Meme Transfer Our greatest fragility? Meme Many human beliefs are: False Unhealthy Masculinity Compassion Masculinity Compassion

225. Horizontal Transfer Constrained Deconstrained Universal architectures Universal laws Fast Slow Flexible Inflexible General Special SW Apps OS HW