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    Introduction to genomics / Arthur Lesk.

    • Title:Introduction to genomics / Arthur Lesk.
    •    
    • Author/Creator:Lesk, Arthur M., author.
    • Published/Created:Oxford : Oxford University Press, [2017]
    • Holdings

       
    • Library of Congress Subjects:Genomics.
    • Medical Subjects: Genomics.
    • Edition:Third edition.
    • Description:xxvii, 509 pages : illustrations (colour), maps (colour) ; 27 cm
    • Summary:"Our genome is the blueprint for our existence: it encodes all the information we need to develop from a single cell into a hugely complicated functional organism. Yet it is more than a static information store: our genome is a dynamic, tightly-regulated collection of genes, which switch on and off in many combinations to give the variety of cells from which our bodies are formed. But how do we identify the genes that make up our genome? How do we determine their function? And how do different genes form the regulatory networks that direct the processes of life? Introduction to Genomics is the most up-to-date and complete textbook for students approaching the subject for the first time. Lesk's engaging writing style brings a narrative to a disparate field of study and offers a fascinating insight into what can be revealed from the study of genomes. The book covers: the similarities and differences between organisms; how different organisms evolved; how the genome is constructed and how it operates; and what our understanding of genomics means in terms of our future health and wellbeing."--Provided by publisher.
    • Notes:Previous edition: 2012.
      Includes bibliographical references and index.
    • ISBN:9780198754831 paperback
      0198754833 paperback
    • Contents:Machine generated contents note: Learning goals
      Genomics: the hub of biology
      Phenotype = genotype + environment + life history + epigenetics
      Varieties of genome organization
      Chromosomes, organelles, and plasmids
      Genes
      scope and applications of genome sequencing projects
      Variations in genome sequences within species
      Mutations and disease
      Single-nucleotide polymorphisms
      Haplotypes
      clinically important haplotype: the major histocompatibility complex
      Populations
      Species
      biosphere
      Extinctions
      future?
      Genome projects and our current library of genome information
      High-throughput sequencing
      De novo sequencing
      Resequencing
      Exome sequencing
      What's in a genome?
      Some regions of the genome encode non-protein-coding RNA molecules
      Some regions of the genome contain pseudogenes
      Other regions contain binding sites for ligands responsible for regulation of transcription
      Repetitive elements of unknown function account for surprisingly large fractions of our genomes
      Dynamic components of genomes
      Genomics and developmental biology
      Genes and minds: neurogenomics
      Genetics of behaviour
      Proteomics
      Protein evolution: divergence of sequences and structures within and among species
      Mechanisms of protein evolution
      Organization and regulation
      Some mechanisms of regulation act at the level of transcription
      Some mechanisms of regulation act at the level of translation
      Some regulatory mechanisms affect protein activity
      On the web: genome browsers
      Genomics and computing
      Archiving and analysis of genome sequences and related data
      Databanks in molecular biology
      Programming
      Looking forward
      Recommended reading
      Exercises and problems
      Learning goals
      '...the end of the beginning'
      Human genome sequencing
      What makes us human?
      Comparative genomics
      Genomics and language
      human genome and medicine
      Prevention of disease
      Detection and precise diagnosis
      Genetic counselling-carrier status
      Discovery and implementation of effective treatment
      Tunable healthcare delivery: pharmacogenomics
      'Pop' applications of genome sequencing
      Genomics in personal identification
      DNA 'fingerprinting'
      Personal identification by amplification of specific regions has superseded the RFLP approach
      Mitochondrial DNA
      Analysis of non-human DNA sequences
      Parentage testing
      Inference of physical features, and even family name
      Ethical, legal, and social issues
      Databases containing human DNA sequence information
      Use of DNA sequencing in research on human subjects
      Looking forward
      Recommended reading
      Exercises and problems
      Learning goals
      Classical genetics as background
      What is a gene?
      Maps and tour guides
      Genetic maps
      Linkage
      Linkage disequilibrium
      Chromosome banding pattern maps
      Restriction maps
      Discovery of the structure of DNA
      DNA sequencing
      Frederick Sanger and the development of DNA sequencing
      DNA sequencing by termination of chain replication
      Maxam-Gilbert chemical cleavage method
      Automation of DNA sequencing
      Organizing a large-scale sequencing project
      Bring on the clones: hierarchical-or 'BAC-to-BAC'-genome sequencing
      Whole-genome shotgun sequencing
      Next-generation sequencing
      Roche 454 Life Sciences
      Illumina
      Ion Torrent/Personal Genome Machine (PGM)
      PacBio
      Oxford Nanopore
      10X Genomics
      Biohano Irys system
      Life in the fast lane
      How much sequencing power is there in the world?
      Databanks in molecular biology
      Nucleic acid sequence databases
      Protein sequence databases
      Databases of genetic diseases-OMIM and OMIA
      Databases of structures
      Specialized or 'boutique' databases
      Expression and proteomics databases
      Databases of metabolic pathways
      Bibliographic databases
      Surveys of molecular biology databases and servers
      Computer programming in genomics
      Programming languages
      How to compute effectively
      Looking forward
      Recommended reading
      Exercises and problems
      Learning goals
      Evolution is exploration
      Biological systematics
      Biological nomenclature
      Measurement of biological similarities and differences
      Homologues and families
      Pattern matching-the basic tool of bioinformatics
      Sequence alignment
      Defining the optimum alignment
      Scoring schemes
      Varieties and extensions
      Approximate methods for quick screening of databases
      Pattern matching in three-dimensional structures
      Evolution of protein sequences, structures, and functions
      Evolution of protein structure and function
      Phylogeny
      Calculation of phylogenetic trees
      Short-circuiting evolution: genetic engineering
      Looking forward
      Recommended reading
      Exercises and problems
      Learning goals
      Evolution and phylogenetic relationships in prokaryotes
      Major types of prokaryotes
      Do we know the root of the tree of life?
      Genome organization in prokaryotes
      Replication and transcription
      Gene transfer
      Archaea
      genome of Methanococcus jannaschn
      Life at extreme temperatures
      Comparative genomics of hyperthermophilic archaea: Thermococcus kodakarensis and pyrococci
      Bacteria
      Genomes of pathogenic bacteria
      Genomics and the development of vaccines
      Viruses
      Nucleocytoplasmic large DNA viruses (or giant viruses)
      Viral genomes
      Recombinant viruses
      Viruses and evolution
      Influenza: a past and current threat
      'Ome, 'ome, on the range: metagenomics, the genomes in a coherent environmental sample
      Marine cyanobacteria-an in-depth study
      Looking forward
      Recommended reading
      Exercises and problems
      Learning goals
      origin and evolution of eukaryotes
      Evolution and phylogenetic relationships in eukaryotes
      yeast genome
      evolution of plants
      Arabidopsis thaliana genome
      Genomes of animals
      genome of the sea squirt (Ciona intestinalis)
      genome of the pufferfish (Tetraodon nigroviridis)
      genome of the chicken (Gallus gallus domesticus)
      genome of the platypus (Ornithorhynchus anatinus)
      genome of the dog
      Palaeosequencing-ancient DNA
      Recovery of DNA from ancient samples
      DNA from extinct birds
      High-throughput sequencing of mammoth DNA
      phylogeny of elephants
      Looking forward
      Recommended reading
      Exercises and problems
      Learning goals
      Introduction
      Unity and diversity of life
      Taxonomy based on sequences
      Sizes and organization of genomes
      Genome sizes
      Genome organization in eukaryotes
      Photosynthetic sea slugs: endosymbiosis of chloroplasts
      How genomes differ
      Variation at the level of individual nucleotides
      Duplications
      Duplication of genes
      Family expansion: G protein-coupled receptors
      Comparisons at the chromosome level: synteny
      What makes us human?
      Comparative genomics
      Genomes of chimpanzees and humans
      Genomes of mice and rats
      Model organisms for study of human diseases
      genome of Caenorhabditis elegans
      genome of Drosophila melanogaster
      Homologous genes in humans, worms, and flies
      Looking forward
      Recommended reading
      Exercises and problems
      Learning goals
      Introduction
      Some diseases are associated with mutations in specific genes
      Haemoglobinopathies-molecular diseases caused by abnormal haemoglobins
      Phenylketonuria
      Alzheimer's disease
      Identification of genes associated with inherited diseases
      Genome-wide association studies
      GWAS of sickle-cell disease
      GWAS of type 2 diabetes
      GWAS of schizophrenia
      human microbiome
      Treatment of abnormal microbiome composition
      Cancer genomics
      SNPs and cancer
      Whole-genome sequencing association studies of breast cancer
      Copy-number alterations in cancer
      Chromosomal aberrations
      Epigenetics and cancer
      microRNAs and cancer
      Immunotherapy for cancer
      Looking forward
      Recommended reading
      Exercises and problems
      Learning goals
      Ancestry of Homo sapiens
      Neanderthal genome
      Denisovan genome
      What do these data tell us?
      What have Neanderthals and Denisovans done for us lately?
      Ancient populations and migrations
      Western civilization? 'I think it would be a good idea'
      Domestication of the dog
      Domestication of the horse
      Domestication of crops
      Maize (Zea mays)
      Rice (Oryza sativa)
      Control of flowering time
      History of rice domestication
      Chocolate (Theobroma cacao)
      Theobroma cacao genome
      Looking forward
      Recommended reading
      Exercises and problems
      Learning goals
      Introduction
      Microarrays
      Microarray data are semiquantitative
      Applications of DNA microarrays
      Analysis of microarray data
      RNAseq
      RNAseq versus microarrays
      Expression patterns in different physiological states
      Sleep in rats and fruit flies
      Expression pattern changes in development
      Variation of expression patterns during the life cycle of Drosophila melanogaster
      Flower formation in roses
      Expression patterns in learning and memory: long-term potentiation
      Conserved clusters of co-expressing genes
      Evolutionary changes in expression patterns
      Applications of transcriptomics in medicine
      Development of antibiotic resistance in bacteria
      Childhood leukaemias
      Encyclopedia of DNA Elements (ENCODE)
      Looking forward
      Recommended reading
      Exercises and problems
      Learning goals
      Introduction
      Protein nature and types of proteins
      Contents note continued: Protein structure
      chemical structure of proteins
      Conformation of the polypeptide chain
      Protein folding patterns
      Domains
      Disorder in proteins
      Post-translational modifications
      Why is there a common genetic code with 20 canonical amino acids?
      Separation and analysis of proteins
      Polyacrylamide gel electrophoresis (Page)
      Two-dimensional Page
      Mass spectrometry
      Identification of components of a complex mixture
      Protein sequencing by mass spectrometry
      Quantitative analysis of relative abundance
      Measuring deuterium exchange in proteins
      Experimental methods of protein structure determination
      X-ray crystallography of proteins
      Interpretation of the electron density: model building and improvement
      How accurate are the structures?
      NMR spectroscopy in structural biology
      Protein structure determination by NMR
      Low-temperature electron microscopy (cryoEM)
      Classifications of protein structures
      SCOP
      SCOP2
      Protein complexes and aggregates
      Protein aggregation diseases
      Properties of protein-protein complexes
      Stoichiometry-what is the composition of the complex?
      Affinity-how stable is the complex?
      How are complexes organized in three dimensions?
      Multisubunit proteins
      Many proteins change conformation as part of the mechanism of their function
      Conformational change during enzymatic catalysis
      Motor proteins
      Allosteric regulation of protein function
      Allosteric changes in haemoglobin
      Conformational states of serine protease inhibitors (serpins)
      Protein structure prediction and modelling
      Homology modelling
      Secondary structure prediction
      Prediction of novel folds: ROSETTA
      Available protocols for protein structure prediction
      Structural genomics
      Directed evolution and protein design
      Directed evolution of subtilisin E
      Looking forward
      Recommended reading
      Exercises and problems
      Learning goals
      Introduction
      Classification and assignment of protein function
      Enzyme Commission
      Gene Ontology[™] Consortium protein function classification
      Comparison of EC and GO classifications
      Metabolic networks
      Databases of metabolic pathways
      EcoCyc
      Kyoto Encyclopedia of Genes and Genomes
      Human Metabolome Database
      Evolution and phylogeny of metabolic pathways
      Alignment and comparison of metabolic pathways
      Comparing linear metabolic pathways
      Reconstruction of metabolic networks
      Comparing non-linear metabolic pathways: the pentose phosphate pathway and the Calvin-Benson cycle
      Metabolomics in ecology
      Dynamic modelling of metabolic pathways
      Looking forward
      Recommended reading
      Exercises and problems
      Learning goals
      Introduction
      Regulatory mechanisms
      Two parallel networks: physical and logical
      Networks and graphs
      Robustness and redundancy
      Connectivity in networks
      Dynamics, stability, and robustness
      Protein complexes and aggregates
      Protein interaction networks
      Protein-DNA interactions
      DNA-protein complexes
      Structural themes in protein-DNA binding and sequence recognition
      Bacteriophage T7 DNA polymerase
      Some protein-DNA complexes that regulate gene transcription
      Regulatory networks
      Structures of regulatory networks
      Structural biology of regulatory networks
      Gene regulation
      transcriptional regulatory network of Escherichia coli
      genetic switch of bacteriophage X
      Regulation of the lactose operon in Escherichia coli
      genetic regulatory network of Saccharomyces cerevisiae
      Adaptability of the yeast regulatory network
      Looking forward
      Recommended reading
      Exercises and problems
      Prologue: Preliminaries
      0.1. Signpost: Uncertainty
      0.2. Discrete Probability Distributions
      0.2.1. probability distribution summarizes our knowledge about an uncertain situation
      0.2.2. Conditional probability quantifies the degree to which events are correlated
      0.2.3. random variable can be partially described by its expectation and variance
      0.2.4. Joint distributions
      0.2.5. Some explicit discrete distributions
      0.3. Dimensional Analysis
      0.4. Continuous Probability Distributions
      0.4.1. Probability density functions
      0.4.2. Some explicit continuous distributions
      0.5. More Properties of, and Operations on, Probability Distributions
      0.5.1. Transformation of a probability density function
      0.5.2. sample mean of many independent, identically distributed random variables has lower variance than any one of its constituents
      0.5.3. Count data are typically Poisson distributed
      0.5.4. difference of two noisy quantities can have greater relative standard deviation than either by itself
      0.5.5. convolution of two distributions describes the sum of their random variables
      0.6. Thermal Randomness
      Big Picture
      Key Formulas
      Problems
      ch. 1 What Is Light?
      1.1. Signpost: Photons
      1.2. Light Before 1905
      1.2.1. Basic light phenomena
      1.2.2. Light displays wavelike behavior in many situations
      1.3. Light Is Lumpy
      1.3.1. discrete aspect of light is most apparent at extremely low intensity
      1.3.2. photoelectric effect
      1.3.3. Einstein's proposal
      1.3.4. Light-induced phenomena in biology qualitatively support the Einstein relation
      1.4. Background: Poisson Processes
      1.4.1. Poisson process can be defined as a continuous-time limit of repeated Bernoulli trials
      1.4.2. Blip counts in a fixed interval are Poisson distributed
      1.4.3. Waiting times are Exponentially distributed
      1.5. New Physical Model of Light
      1.5.1. Light Hypothesis, part 1
      1.5.2. spectrum of light can be regarded as a probability density times an overall rate
      1.5.3. Light can eject electrons from individual molecules, inducing photochemical reactions
      1.6. Fluorescence and Photoisomerization Can Occur after Photon Absorption
      1.6.1. Electron State Hypothesis
      1.6.2. Atoms have sharp spectral lines
      1.6.3. Molecules: fluorescence
      1.6.4. Molecules: photoisomerization
      1.7. Transparent Media Are Unchanged by the Passage of Light, but Slow It Down
      Big Picture
      Key Formulas
      1.3.1. Quantum randomness is distinct from classical chaos
      1.3.3.a. reality of photons
      1.3.3.b. Light also carries momentum
      1.3.3.c. thermal radiation spectrum
      1.3.3.d. role of frequency
      1.4. Corrections to Poisson emission and detection
      1.5.1.a. Gamma rays
      1.5.1.b. More about the Light Hypothesis
      1.5.3. Mechanism of DNA photodamage
      1.6.1. Dense media
      1.6.2.a. More about atoms and light
      1.6.2.b. Cauchy distribution in physics
      1.6.3.a. Born-Oppenheimer approximation
      1.6.3.b. Classical approximation for nuclear motion
      1.6.3.c. Debye relaxation
      1.6.4. Fast conformational changes
      Problems
      ch. 2 Photons and Life
      2.1. Signpost: Seeing and Touching
      2.2. Light-Induced DNA Damage
      2.3. Fluorescence as a Window into Cells
      2.3.1. Fluorescence can discriminate healthy from diseased tissue during surgery
      2.3.2. Fluorescence microscopy can reduce background and specifically show only objects of interest
      2.4. Background: Membrane Potential
      2.4.1. Electric currents involve ion motion
      2.4.2. ion imbalance across the cell membrane can create a membrane potential
      2.4.3. Ion pumps maintain a resting electric potential drop across the cell membrane
      2.4.4. Ion channels modulate the membrane potential to implement neural signaling
      2.4.5. Action potentials can transmit information over long distances
      2.4.6. Creation and utilization of action potentials
      2.4.7. More about synaptic transmission
      2.5. Optogenetics
      2.5.1. Brains are hard to study
      2.5.2. Channelrhodopsin can depolarize selected neurons in response to light
      2.5.3. Halorhodopsin can hyperpolarize selected neurons in response to light
      2.5.4. Other methods
      2.6. Fluorescent Reporters Can Give Real-Time Readout of Cellular Conditions
      2.6.1. Voltage-sensitive fluorescent reporters
      2.6.2. Split fluorescent proteins and genetically encoded calcium indicators
      2.7. Two-Photon Excitation Permits Imaging Deep within Living Tissue
      2.7.1. problem of imaging thick samples
      2.7.2. Two-photon excitation depends sensitively on light intensity
      2.7.3. Multiphoton microscopy can excite a specific volume element of a specimen
      2.8. Fluorescence Resonance Energy Transfer
      2.8.1. How to tell when two molecules are close to each other
      2.8.2. physical model for FRET
      2.8.3. Some forms of bioluminescence also involve FRET
      2.8.4. FRET can be used to create a spectroscopic "ruler"
      2.8.5. Application of FRET to DNA bending flexibility
      2.8.6. FRET-based indicators
      2.9. Glimpse of Photosynthesis
      2.9.1. It's big
      2.9.2. Two quantitative puzzles advanced our understanding of photosynthesis
      2.9.3. Resonance energy transfer resolves both puzzles
      Big Picture
      Key Formulas
      2.4.3. More about membrane potentials
      2.4.5. Other uses for the resting potential
      2.7.2. beta-squared rule
      2.7.3. More about two-photon imaging
      2.8.1. About FRET and its efficiency
      2.8.4. Other experimental tests of FRET
      2.8.5. Why reported FRET efficiencies sometimes exceed 100%
      2.9.3. More details about the photosynthesis apparatus in plants
      Problems
      ch. 3 Color Vision
      3.1. Signpost: A Fifth Dimension
      3.2. Color Vision Confers a Fitness Payoff
      Contents note continued: 3.3. Newton's Experiments on Color
      3.4. Background: More Properties of Poisson Processes
      3.4.1. Thinning property
      3.4.2. Merging property
      3.4.3. Significance for light
      3.5. Combining Two Beams Corresponds to Summing Their Spectra
      3.6. Psychophysical Aspects of Color
      3.6.1. R+G looks like Y
      3.6.2. Color discrimination is many-to-one
      3.6.3. Perceptual matching follows quantitative, reproducible, and context-independent rules
      3.7. Color from selective absorption
      3.7.1. Reflectance and transmittance spectra
      3.7.2. Subtractive color scheme
      3.8. Physical Model of Color Vision
      3.8.1. color-matching function challenge
      3.8.2. Available wetware in the eye
      3.8.3. trichromatic model
      3.8.4. trichromatic model explains why R+a~,Y
      3.8.5. Our eyes project light spectra to a 3D vector space
      3.8.6. mechanical analogy for color matching
      3.8.7. Connection between the mechanical analogy and color vision
      3.8.8. Quantitative comparison to experimentally observed color-matching functions
      3.9. Why the Sky Is Not Violet
      3.10. Direct Imaging of the Cone Mosaic
      Big Picture
      Key Formulas
      3.5.a. Flux, irradiance, and spectral flux irradiance
      3.5.b. Combining spectra is a linear operation
      3.6.3.a. Variation of color matching
      3.6.3.b. Colorblindness
      3.6.3.c. Tetrachromacy
      3.7. Perceptual color
      3.8.3.a. Determination of sensitivity functions
      3.8.3.b. Contrast to audition
      3.8.4.a. Enhancement of color contrast in autofluorescence endoscopy
      3.8.4.b. Spectral analysis can discriminate many fluorophores and their combinations
      3.8.5.a. Photoisomerization rate regarded as an inner product
      3.8.5.b. Correction to predicted color matching due to absorption
      3.8.8.a. Relative versus absolute sensitivity
      3.8.8.b. Simplified color space
      Problems
      ch. 4 How Photons Know Where to Go
      4.1. Signpost: Probability Amplitudes
      4.2. Summary of Key Phenomena
      4.3. Probability Amplitude
      4.3.1. Reconciling the particle and wave aspects of light requires the introduction of a new kind of physical quantity
      4.4. Background: Complex Numbers Simplify Many Calculations
      4.5. Light Hypothesis, part 2
      4.6. Basic Interference Phenomena
      4.6.1. Two-slit interference explained via the Light Hypothesis
      4.6.2. Newton's rings illustrate interference in a three-dimensional setting
      4.6.3. objection to the Light Hypothesis
      4.7. Stationary-Phase Principle
      4.7.1. Fresnel integral illustrates the stationary-phase principle
      4.7.2. probability amplitude is computed as a sum over all possible photon paths
      4.7.3. Diffraction through a single, wide aperture
      4.7.4. Reconciliation of particle and wave aspects
      Big Picture
      Key Formulas
      4.2. On philosophically repugnant theories
      4.5.a. More about the Light Hypothesis
      4.5.b. More about uniform media
      4.6.1. Which slit?
      4.6.2. More about reflection
      4.6.3. More objections
      4.7.2.a. neighborhood of the stationary-phase path
      4.7.2.b. Nonuniform media
      Problems
      ch. 5 Optical Phenomena and Life
      5.1. Signpost: Sorting and Directing
      5.2. Structural Color in Insects, Birds, and Marine Organisms
      5.2.1. Some animals create color by using nanostructures made from transparent materials
      5.2.2. extension of the Light Hypothesis describes reflection and transmission at an interface
      5.2.3. single thin, transparent layer reflects with weak wavelength dependence
      5.2.4. stack of many thin, transparent layers can generate an optical bandgap
      5.2.5. Structural color in marine organisms
      5.3. Ray-optics Phenomena
      5.3.1. reflection law is a consequence of the stationary-phase principle
      5.3.2. Transmission and reflection gratings generate non-ray-optics behavior by editing the set of allowed photon paths
      5.3.3. Refraction arises from the stationary-phase principle applied to a piecewise-uniform medium
      5.3.4. Total internal reflection provides another tool to enhance signal relative to noise in fluorescence microscopy
      5.3.5. Refraction is generally wavelength dependent
      Big Picture
      Key Formulas
      5.2.2. Transmission and reflection in classical electromagnetism
      5.3.1. Fine points about reflection and refraction
      5.2.4. More complicated layers
      Problems
      ch. 6 Direct Image Formation
      6.1. Signpost: Bright Yet Sharp
      6.2. Image Formation Without Lenses
      6.2.1. Shadow imaging
      6.2.2. Pinhole imaging suffices for some animals
      6.3. Addition of a Lens Allows Formation of Bright, Yet Sharp, Images
      6.3.1. focusing criterion relates object and image distances to lens shape
      6.3.2. more general approach
      6.3.3. Formation of a complete image
      6.3.4. Aberration degrades image formation outside the paraxial limit
      6.4. Vertebrate Eye
      6.4.1. Image formation with an air-water interface
      6.4.2. Focusing powers add in a compound lens system
      6.4.3. deformable lens implements focal accommodation
      6.5. Light Microscopes and Related Instruments
      6.5.1. "Rays of light" are a useful idealization in the ray-optics regime
      6.5.2. Real and virtual images
      6.5.3. Spherical aberration
      6.5.4. Dispersion gives rise to chromatic aberration
      6.5.5. Confocal microscopy suppresses out-of-focus background light
      6.6. Darwin's Difficulty
      6.7. Background: Angles and Angular Area
      6.7.1. Angles
      6.7.2. Angular area
      6.8. Diffraction Limit
      6.8.1. Even a perfect lens will not focus light perfectly
      6.8.2. Three dimensions: The Rayleigh criterion
      6.8.3. Animal eyes match their photoreceptor size to the diffraction limit
      Big Picture
      Key Formulas
      6.4. retinal pigment epithelium
      6.8.2. Abbe criterion
      Problems
      ch. 7 Imaging as Inference
      7.1. Signpost: Information
      7.2. Background: On Inference
      7.2.1. Bayes formula tells how to update a probability estimate
      7.2.2. Inference with a Uniform prior reduces to likelihood maximization
      7.2.3. Inferring the center of a distribution
      7.2.4. Parameter estimation and credible intervals
      7.2.5. Binning data reduces its information content
      7.3. Localization of a Single Fluorophore
      7.3.1. Localization is an inference problem
      7.3.2. Formulation of a probabilistic model
      7.3.3. Maximum-likelihood analysis of image data
      7.3.4. Results for molecular motor stepping
      7.4. Localization Microscopy
      7.5. Defocused Orientation Imaging
      Big Picture
      Key Formulas
      7.3.2.a. Airy point spread function
      7.3.2.b. Anisotropic point spread function
      7.3.2.c. Other tacit assumptions
      7.3.3. Advantages of the maximum likelihood method
      7.3.4. Background estimation
      7.4. Interferometric PALM imaging
      7.5. More about anisotropy
      Problems
      ch. 8 Imaging by X-Ray Diffraction
      8.1. Signpost: Inversion
      8.2. It's Hard to See Atoms
      8.3. Diffraction Patterns
      8.3.1. periodic array of narrow slits creates a diffraction pattern of sharp lines
      8.3.2. Generalizations to the setup needed to handle x-ray crystallography
      8.3.3. array of slits with substructure gives a diffraction pattern modulated by a form factor
      8.3.4. 2D "crystal" yields a 2D diffraction pattern
      8.3.5. 3D crystals can be analyzed by similar methods
      8.4. Diffraction Pattern of DNA Encodes Its Double-Helical Character
      8.4.1. helical pitch, base pair rise, helix offset, and diameter of DNA can be obtained from its diffraction pattern
      8.4.2. Accurate determination of size parameters led to a breakthrough on the puzzle of DNA structure and function
      Big Picture
      Key Formulas
      8.3.3. Factorization of amplitudes
      8.4.1.a. How to treat fiber samples of DNA
      8.4.1.b. phase problem
      Problems
      ch. 9 Vision in Dim Light
      9.1. Signpost: Construction
      9.2. Edge of Vision
      9.2.1. Many ecological niches are dimly lit
      9.2.2. single-photon challenge
      9.2.3. Measures of detector performance
      9.3. Psychophysical Measurements of Human Vision
      9.3.1. probabilistic character of vision is most evident under dim-light conditions
      9.3.2. Rod cells must be able to respond to individual photon absorptions
      9.3.3. eigengrau hypothesis states that true photon signals are merged with a background of spontaneous events
      9.3.4. Forced-choice experiments characterize the dim-light response
      9.3.5. Questions raised by psychophysical experiments
      9.4. Single-Cell Measurements
      9.4.1. Vertebrate photoreceptors can be monitored via the suction pipette method
      9.4.2. Determination of threshold, quantum catch, and spontaneous signaling rate
      9.4.3. Direct confirmation that the rod cell imposes no threshold
      9.4.4. Additional single-cell results
      9.4.5. Questions raised by the single-cell measurements
      Big Picture
      Key Formulas
      9.4.2.a. fraction of light absorbed by a sample depends exponentially on thickness
      9.4.2.b. quantum yield for rod signaling
      9.4.2.c. Quantum catch for a single human rod cell under axial illumination
      9.4.2.d. whole-retina quantum catch is the product of several factors
      Problems
      ch. 10 Mechanism of Visual Transduction
      10.1. Signpost: Dynamic Range
      10.2. Photoreceptors
      10.2.1. Photoreceptors are a specialized class of neurons
      10.2.2. Each rod cell simultaneously monitors one hundred million rhodopsin molecules
      10.3. Background: Cellular Control and Transduction Networks
      Contents note continued: 10.3.1. Cells can control enzyme activities via allosteric modulation
      10.3.2. Single-cell organisms can alter their behavior in response to environmental cues, including light
      10.3.3. two-component signaling pathway motif
      10.3.4. Network diagrams summarize complex reaction networks
      10.3.5. Cooperativity can increase the sensitivity of a network element
      10.4. Photon Response Events Localized to One Disk
      10.4.1. Step 1: photoisomerization of rhodopsin in the disk membrane
      10.4.2. Step 2: activation of transducin in the disk membrane
      10.4.3. Steps 3-4: activation of phosphodiesterase in the disk membrane, and hydrolysis of cyclic GMP in the cytosol
      10.5. Events Elsewhere in the Rod Outer Segment
      10.5.1. Ion pumps in the rod cell plasma membrane maintain nonequilibrium ion concentrations
      10.5.2. Step 5: ion channel closing in the plasma membrane
      10.6. Events at the Synaptic Terminal
      10.6.1. Step 6: hyperpolarization of the plasma membrane
      10.6.2. Step 7: modulation of neurotransmitter release into the synaptic cleft
      10.7. Summary of the Visual Cascade
      Big Picture
      Key Formulas
      10.2.2. Higher light intensities
      10.3.3.a. More about two-component signaling pathways
      10.3.3.b. Phototaxis
      10.3.4. More about adaptation in chemotaxis
      10.4.1. Cone and cone bipolar cells
      10.4.3. Recently discovered vertebrate photoreceptors
      10.6. Glutamate removal
      10.7.a. Termination of the photoreceptor response
      10.7.b. Negative feedback implements adaptation and standardizes signals from rod cells
      10.7.c. Recycling of retinal
      Problems
      ch. 11 First Synapse and Beyond
      11.1. Signpost: False Positives
      11.2. Transmission at the First Synapse
      11.2.1. synapse from rod to rod bipolar cells inverts its signal via another G protein cascade
      11.2.2. first synapse also rejects rod signals below a transmission breakpoint
      11.3. Synthesis of Psychophysics and Single-Cell Physiology
      11.3.1. Why does vision require several captured photons?
      11.3.2. Review of the eigengrau hypothesis
      11.3.3. Single-rod measurements constrain the fit parameters in the eigengrau model
      11.3.4. Processing beyond the first synapse is highly efficient
      11.4. Multistep Relay Sends Signals on to the Brain
      11.4.1. classical rod pathway implements the single-photon response
      11.4.2. Other signaling pathways
      11.4.3. Optogenetic retinal prostheses
      11.5. Evolution and Vision
      11.5.1. Darwin's difficulty, revisited
      11.5.2. Parallels between vision, olfaction, and hormone reception
      Big Picture
      Key Formulas
      11.2.2.a. Instrumental noise
      11.2.2.b. Quantal release noise
      11.2.2.c. Mechanism of discrimination at the first synapse
      11.2.2.d. Why discrimination at the first synapse is advantageous
      11.2.2.e. Thresholding at later stages of processing
      11.3.4. Psychophysics with single photon stimuli
      11.4.1.a. ON and OFF pathways
      11.4.1.b. Image processing in the retina
      11.5.1. Rhabdomeric photoreceptors
      Problems
      ch. 12 Electrons, Photons, and the Feynman Principle
      12.1. Signpost: Universality
      12.2. Electrons
      12.2.1. From paths to trajectories
      12.2.2. action functional singles out classical trajectories as its stationary points
      12.2.3. Feynman principle expresses probability amplitudes as sums over trajectories
      12.2.4. States and operators arise from partial summation over trajectories
      12.2.5. Stationary states are invariant under time evolution
      12.2.6. confined-electron problem
      12.2.7. Light absorption by ring-shaped molecules
      12.2.8. Schrodinger equation emerges in the limit of an infinitesimal time step
      12.3. Photons
      12.3.1. action functional for photon trajectories
      12.3.2. special case of a monochromatic light source reduces to our earlier formulation
      12.3.3. Vista: reflection, transmission, and the index of refraction
      Big Picture
      ch. 13 Field Quantization, Polarization, and the Orientation of a Single Molecule
      13.1. Signpost: Fields
      13.2. Single Molecule Emits Photons in a Dipole Distribution
      13.3. Classical Field Theory of Light
      13.4. Quantization Replaces Field Variables by Operators
      13.5. Photon States
      13.5.1. Basis states can be formed by applying creation operators to the vacuum state
      13.5.2. Coherent states mimic classical states in the limit of large occupation numbers
      13.6. Interaction with Electrons
      13.6.1. Classical interactions involve adding source terms to the field equations
      13.6.2. Electromagnetic interactions can be treated perturbatively
      13.6.3. dipole emission pattern
      13.6.4. Electrons and positrons can also be created and destroyed
      13.7. Vistas
      13.7.1. Connection to the approach used in earlier chapters
      13.7.2. Some invertebrates can detect the polarization of light
      13.7.3. Invertebrate photoreceptors have a different morphology from vertebrates
      13.7.4. Polarized light must be used for single photoreceptor measurements
      13.7.5. Some transitions are far more probable than others
      13.7.6. Lasers exploit a preference for emission into an already occupied state
      13.7.7. Fluorescence polarization anisotropy
      Big Picture
      ch. 14 Quantum-Mechanical Theory of FRET
      14.1. Signpost: Decoherence
      14.2. Two-state Systems
      14.2.1. FRET displays both classical and quantum aspects
      14.2.2. isolated two-state system oscillates in time
      14.2.3. Environmental effects modify the behavior of a two-state system in solution
      14.2.4. density operator summarizes the effect of the environment
      14.2.5. Time development of the density operator
      14.3. FRET
      14.3.1. weakly coupled, strongly incoherent limit displays first-order kinetics
      14.3.2. Forster's formula arises in the electric dipole approximation
      14.3.3. More realistic treatment of the role of FRET in photosynthesis
      Big Picture
      A.1. Mathematical Notation
      A.2. Network Diagrams
      A.3. Named Quantities
      B.1. Base Units
      B.2. Dimensions Versus Units
      B.3. About Graphs
      B.3.1. Arbitrary units
      B.3.2. Angles
      B.4. Payoff
      C.1. Fundamental Constants
      C.2. Optics
      C.2.1. Index of refraction for visible light
      C.2.2. Miscellaneous
      C.3. Eyes
      C.3.1. Geometric
      C.3.2. Rod cells
      C.3.3. Cone cells
      C.3.4. Beyond photoreceptors
      C.4. B-Form DNA.
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