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

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

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

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

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

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

Fast Slow VOR vision Why? Mechanism Tradeoff Cerebellum

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

Slow Flexible vision eye vision Act slow delay Fast Inflexible

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

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

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

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

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

eye vision Act VOR Layering Automatic Unconscious Partially Conscious Cerebellum

eye vision Act slow delay VOR fast Layering Feedback

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

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

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

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

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)

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

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

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

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

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

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

Stare at the intersection

Stare at the intersection.

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

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

gradient Biased random walk Ligand Signal Transduction MotionMotor CheY

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

Slow Flexible vision Fast Inflexible VOR color vision Layering Distributed Feedback

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

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

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

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

Slow Flexible vision Fast Inflexible VOR color vision Layering Distributed Feedback

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)

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

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

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

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

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

eye vision Act delay Control noise error

eye vision Act delay Control noise error easy hard

eye vision Act delay Control noise error easy hard

eye vision Act delay Control noise error Close one eye?

Length, m too fragile complex No tradeoff expensive fragile Slow Flexible vision eye vision Act slow delay Fast Inflexible VOR fast Universal laws?

Length, m Slow Flexible vision eye vision Act slow delay Fast Inflexible VOR fast How do these fit together?

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

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

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

delay sec/m area.1110 diam(  m) 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

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

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

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

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

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

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

slow flexible fast inflexible In general? wastefulefficient fragile robust

slow flexible fast inflexible fragile robust wasteefficient fragile robust

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

slow flexible fast inflexible waste efficient fragile robust Cyber-physical

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

slow flexible fast inflexible waste efficient

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

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

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

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

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

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

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

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

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

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

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

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

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

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)

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

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

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

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

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

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

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

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

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

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?

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”

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

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?

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

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

Slow Flexible vision Fast Inflexible VOR

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

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

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

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

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

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

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

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)

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

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

When needed, even wasps can do it.

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.

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

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

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

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

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”

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

costly fragile efficient robust Learning

crawl walk bike Learning

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

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

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

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

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

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

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

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

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

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.

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

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

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

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

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

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

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

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

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

time What dominates tradeoffs CostlyCheap Fast Slow Energy

time What dominates tradeoffs CostlyCheap Fast Slow Energy Flexible Inflexible

time What dominates tradeoffs Fast Slow Flexible Inflexible

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

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

Length, m 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

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”

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

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

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

slow flexible fast inflexible waste efficient fragile robust

slow flexible fast inflexible waste efficient body brain Combo

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

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

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

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

Fast Slow Flexible Inflexible General Special Apps OS HW

OS Horizontal App Transfer Horizontal Hardware Transfer Constrained Deconstrained

Horizontal Transfer Constrained Deconstrained

Constrained Deconstrained

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

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

Efficient Robust Evolvable Constrained Deconstrained Diverse

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

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

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

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

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

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

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

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

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

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

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

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

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

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)

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

gradient Biased random walk Ligand Signal Transduction MotionMotor CheY

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

Random walk Ligand MotionMotor Bacterial chemotaxis

gradient Biased random walk Ligand Signal Transduction MotionMotor CheY

Ligand Signal Transduction MotionMotor CheY

Ligand Signal Transduction MotionMotor CheY Component of feedback controller

Ligand MotionMotor CheY TransmitterReceiver Receptor Response Component of feedback controller

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

Transmitter Receiver Motor Variety of receptors & ligands

Ligand MotionMotor CheY Transmitter Receiver Motor Variety of receptors & ligands

CheY TransmitterReceiver Receptor Response Integral feedback internal to signaling network

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

Ligand Signal Transduction MotionMotor CheY

gradient Biased random walk Ligand Signal Transduction MotionMotor CheY

Tumbling bias Signal Transduction Motor Perfect adaptation is necessary … ligand

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

Tumbling bias

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

TransmitterReceiver Variety of Ligands & Receptors Response

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

? 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

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

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

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

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

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.

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

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

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

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

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

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

SenseMotor Fast Reflex Evolve Analog? Most metazoans

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

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

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

Length, m 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

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

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

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

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

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