references.bib

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@ARTICLE{Charlier2021-vq,
  title    = "Kernel Operations on the {GPU}, with Autodiff, without Memory
              Overflows",
  author   = "Charlier, Benjamin and Feydy, Jean and Glaun{\`e}s, Joan Alexis
              and Collin, Fran{\c c}ois-David and Durif, Ghislain",
  journal  = "J. Mach. Learn. Res.",
  volume   =  22,
  number   =  74,
  pages    = "1--6",
  year     =  2021,
  issn     = "1532-4435, 1533-7928"
}

@ARTICLE{Kinz-Thompson2021-tb,
  title    = "Bayesian Inference: The Comprehensive Approach to Analyzing
              {Single-Molecule} Experiments",
  author   = "Kinz-Thompson, Colin D and Ray, Korak Kumar and Gonzalez, Jr,
              Ruben L",
  abstract = "Biophysics experiments performed at single-molecule resolution
              provide exceptional insight into the structural details and
              dynamic behavior of biological systems. However, extracting this
              information from the corresponding experimental data
              unequivocally requires applying a biophysical model. In this
              review, we discuss how to use probability theory to apply these
              models to single-molecule data. Many current single-molecule data
              analysis methods apply parts of probability theory, sometimes
              unknowingly, and thus miss out on the full set of benefits
              provided by this self-consistent framework. The full application
              of probability theory involves a process called Bayesian
              inference that fully accounts for the uncertainties inherent to
              single-molecule experiments. Additionally, using Bayesian
              inference provides a scientifically rigorous method of
              incorporating information from multiple experiments into a single
              analysis and finding the best biophysical model for an experiment
              without the risk of overfitting the data. These benefits make the
              Bayesian approach ideal for analyzing any type of single-molecule
              experiment.",
  journal  = "Annu. Rev. Biophys.",
  volume   =  50,
  pages    = "191--208",
  month    =  may,
  year     =  2021,
  language = "en",
  issn     = "1936-122X, 1936-1238",
  pmid     = "33534607",
  doi      = "10.1146/annurev-biophys-082120-103921",
  pmc      = "PMC8238404"
}

@ARTICLE{Ober2015-ba,
  title    = "Quantitative Aspects of Single Molecule Microscopy",
  author   = "Ober, Raimund J and Tahmasbi, Amir and Ram, Sripad and Lin,
              Zhiping and Ward, E Sally",
  abstract = "Single molecule microscopy is a relatively new optical microscopy
              technique that allows the detection of individual molecules such
              as proteins in a cellular context. This technique has generated
              significant interest among biologists, biophysicists and
              biochemists, as it holds the promise to provide novel insights
              into subcellular processes and structures that otherwise cannot
              be gained through traditional experimental approaches. Single
              molecule experiments place stringent demands on experimental and
              algorithmic tools due to the low signal levels and the presence
              of significant extraneous noise sources. Consequently, this has
              necessitated the use of advanced statistical signal and image
              processing techniques for the design and analysis of single
              molecule experiments. In this tutorial paper, we provide an
              overview of single molecule microscopy from early works to
              current applications and challenges. Specific emphasis will be on
              the quantitative aspects of this imaging modality, in particular
              single molecule localization and resolvability, which will be
              discussed from an information theoretic perspective. We review
              the stochastic framework for image formation, different types of
              estimation techniques and expressions for the Fisher information
              matrix. We also discuss several open problems in the field that
              demand highly non-trivial signal processing algorithms.",
  journal  = "IEEE Signal Process. Mag.",
  volume   =  32,
  number   =  1,
  pages    = "58--69",
  month    =  jan,
  year     =  2015,
  language = "en",
  issn     = "1053-5888",
  pmid     = "26167102",
  doi      = "10.1109/MSP.2014.2353664",
  pmc      = "PMC4494126"
}

@ARTICLE{Chiang2021-fi,
  title         = "Named Tensor Notation",
  author        = "Chiang, David and Rush, Alexander M and Barak, Boaz",
  abstract      = "We propose a notation for tensors with named axes, which
                   relieves the author, reader, and future implementers from
                   the burden of keeping track of the order of axes and the
                   purpose of each. It also makes it easy to extend operations
                   on low-order tensors to higher order ones (e.g., to extend
                   an operation on images to minibatches of images, or extend
                   the attention mechanism to multiple attention heads). After
                   a brief overview of our notation, we illustrate it through
                   several examples from modern machine learning, from building
                   blocks like attention and convolution to full models like
                   Transformers and LeNet. Finally, we give formal definitions
                   and describe some extensions. Our proposals build on ideas
                   from many previous papers and software libraries. We hope
                   that this document will encourage more authors to use named
                   tensors, resulting in clearer papers and less bug-prone
                   implementations. The source code for this document can be
                   found at https://github.com/namedtensor/notation/. We invite
                   anyone to make comments on this proposal by submitting
                   issues or pull requests on this repository.",
  month         =  feb,
  year          =  2021,
  url           = "http://arxiv.org/abs/2102.13196",
  journal       = "arXiv",
  eprint        = "2102.13196",
  primaryClass  = "cs.LG",
  arxivid       = "2102.13196"
}

@BOOK{Murphy2022-nc,
  title     = "Probabilistic Machine Learning: An introduction",
  author    = "Murphy, Kevin P",
  editor    = "Dietterich, Thomas and Bishop, Christopher and Heckerman, David
               and Jordan, Michael and Kearns, Michael",
  publisher = "MIT Press",
  year      =  2022,
  address   = "Cambridge",
  isbn      = "10987654321"
}

@ARTICLE{Kingma2014-cz,
  title         = "Adam: A Method for Stochastic Optimization",
  author        = "Kingma, Diederik P and Ba, Jimmy",
  abstract      = "We introduce Adam, an algorithm for first-order
                   gradient-based optimization of stochastic objective
                   functions, based on adaptive estimates of lower-order
                   moments. The method is straightforward to implement, is
                   computationally efficient, has little memory requirements,
                   is invariant to diagonal rescaling of the gradients, and is
                   well suited for problems that are large in terms of data
                   and/or parameters. The method is also appropriate for
                   non-stationary objectives and problems with very noisy
                   and/or sparse gradients. The hyper-parameters have intuitive
                   interpretations and typically require little tuning. Some
                   connections to related algorithms, on which Adam was
                   inspired, are discussed. We also analyze the theoretical
                   convergence properties of the algorithm and provide a regret
                   bound on the convergence rate that is comparable to the best
                   known results under the online convex optimization
                   framework. Empirical results demonstrate that Adam works
                   well in practice and compares favorably to other stochastic
                   optimization methods. Finally, we discuss AdaMax, a variant
                   of Adam based on the infinity norm.",
  month         =  dec,
  year          =  2014,
  url           = "http://arxiv.org/abs/1412.6980",
  journal       = "arXiv",
  eprint        = "1412.6980",
  primaryClass  = "cs.LG",
  arxivid       = "1412.6980"
}

@INCOLLECTION{Van_Vliet1998-jk,
  title     = "Digital fluorescence imaging using cooled {CCD} array cameras
               invisible",
  booktitle = "Cell Biology",
  author    = "van Vliet, L J and Sudar, D and Young, I T",
  editor    = "Celis, J E",
  abstract  = "The progress in solid state technologies has led to a range of
               CCD cameras from inexpensive video cameras to expensive
               scientific digital camera systems. The best choice (best value
               for money) depends heavily on the application. A state-ofthe-art
               camera's performance is limited by the fundamental laws of
               nature. The various noise sources (photon statistics, thermal,
               readout and quantization) are examined to help you understand
               some specific operating conditions such as cooling and the
               choice of readout rates.",
  publisher = "Academic Press",
  volume    =  3,
  pages     = "109--120",
  year      =  1998,
  address   = "New York"
}

@ARTICLE{Stallinga2010-yi,
  title     = "Accuracy of the gaussian point spread function model in {2D}
               localization microscopy",
  author    = "Stallinga, Sjoerd and Rieger, Bernd",
  abstract  = "The gaussian function is simple and easy to implement as Point
               Spread Function (PSF) model for fitting the position of
               fluorescent emitters in localization microscopy. Despite its
               attractiveness the appropriateness of the gaussian is
               questionable as it is not based on the laws of optics. Here we
               study the effect of emission dipole orientation in conjunction
               with optical aberrations on the localization accuracy of
               position estimators based on a gaussian model PSF. Simulated
               image spots, calculated with all effects of high numerical
               aperture, interfaces between media, polarization, dipole
               orientation and aberrations taken into account, were fitted with
               a gaussian PSF based Maximum Likelihood Estimator. For freely
               rotating dipole emitters it is found that the gaussian works
               fine. The same, theoretically optimum, localization accuracy is
               found as if the true PSF were a gaussian, even for aberrations
               within the usual tolerance limit of high-end optical imaging
               systems such as microscopes (Marechal's diffraction limit). For
               emitters with a fixed dipole orientation this is not the case.
               Localization errors are found that reach up to 40 nm for typical
               system parameters and aberration levels at the diffraction
               limit. These are systematic errors that are independent of the
               total photon count in the image. The gaussian function is
               therefore inappropriate, and more sophisticated PSF models are a
               practical necessity.",
  journal   = "Opt. Express",
  publisher = "Optical Society of America",
  volume    =  18,
  number    =  24,
  pages     = "24461--24476",
  month     =  nov,
  year      =  2010,
  language  = "en",
  issn      = "1094-4087",
  pmid      = "21164793",
  doi       = "10.1364/OE.18.024461"
}

@ARTICLE{Haga2011-kh,
  title     = "Dual-view imaging system using a wide-range dichroic mirror for
               simultaneous four-color single-molecule detection",
  author    = "Haga, Takanobu and Takahashi, Satoshi and Sonehara, Tsuyoshi and
               Kumazaki, Nobutaka and Anazawa, Takashi",
  abstract  = "A dual-view imaging system for simultaneous four-color
               single-molecule (SM) detection was developed. As for the
               detection procedure, four species of SM fluorophores, namely,
               Alexa 488, 555, 647, and 680, are immobilized on different
               slides and excited by evanescent-wave illumination. Fluorescence
               emitted from an SM fluorophore is split by a wide-range dichroic
               mirror (WR DM) in a dual-view optics and imaged as two SM
               fluorescence spots (SM spots) on an electron-multiplying
               charge-coupled device (EM-CCD) at 100 Hz. The transmittance of
               the WR DM changes gradually over the wavelength range of 500 to
               700 nm so that the signal ratios of the two SM spots for the
               four fluorophore species differ. A method for classifying SM
               fluorophores into four species in accordance with their signal
               ratios was developed. It was used to classify 597 SM
               fluorophores at an accuracy of above 98\% for all the species.
               This accuracy is comparable to that of a conventional four-color
               SM detection system. To classify four species, the conventional
               system disperses SM fluorescence with a prism and provides an
               elongated SM spot that uses more pixels of an EM-CCD chip than
               that of the developed system. The developed system can thus
               detect 1.5-fold more SM spots with the same-size EM-CCD chip, so
               it can achieve 1.5-fold higher throughput. Moreover, the
               developed system is based on a simple and practical approach,
               namely, replacing an ordinary dichroic mirror in a commercially
               available dual-view optics with a WR DM. This replacement
               transforms a dual-view imaging system for two-color detection
               into a system for four-color detection. The developed system is
               suitable for detection systems of next-generation DNA sequencers
               and DNA microarray-chip analyzers.",
  journal   = "Anal. Chem.",
  publisher = "ACS Publications",
  volume    =  83,
  number    =  18,
  pages     = "6948--6955",
  month     =  sep,
  year      =  2011,
  language  = "en",
  issn      = "0003-2700, 1520-6882",
  pmid      = "21805964",
  doi       = "10.1021/ac2000797"
}

@BOOK{Gelman2013-ro,
  title     = "Bayesian Data Analysis, Third Edition",
  author    = "Gelman, Andrew and Carlin, John B and Stern, Hal S and Dunson,
               David B and Vehtari, Aki and Rubin, Donald B",
  abstract  = "Now in its third edition, this classic book is widely considered
               the leading text on Bayesian methods, lauded for its accessible,
               practical approach to analyzing data and solving research
               problems. Bayesian Data Analysis, Third Edition continues to
               take an applied approach to analysis using up-to-date Bayesian
               methods. The authors---all leaders in the statistics
               community---introduce basic concepts from a data-analytic
               perspective before presenting advanced methods. Throughout the
               text, numerous worked examples drawn from real applications and
               research emphasize the use of Bayesian inference in practice.
               New to the Third Edition Four new chapters on nonparametric
               modeling Coverage of weakly informative priors and
               boundary-avoiding priors Updated discussion of cross-validation
               and predictive information criteria Improved convergence
               monitoring and effective sample size calculations for iterative
               simulation Presentations of Hamiltonian Monte Carlo, variational
               Bayes, and expectation propagation New and revised software code
               The book can be used in three different ways. For undergraduate
               students, it introduces Bayesian inference starting from first
               principles. For graduate students, the text presents effective
               current approaches to Bayesian modeling and computation in
               statistics and related fields. For researchers, it provides an
               assortment of Bayesian methods in applied statistics. Additional
               materials, including data sets used in the examples, solutions
               to selected exercises, and software instructions, are available
               on the book's web page.",
  publisher = "CRC Press",
  series    = "Chapman \& Hall/CRC Texts in Statistical Science",
  edition   =  3,
  month     =  nov,
  year      =  2013,
  address   = "Philadelphia, PA",
  language  = "en",
  isbn      = "9781439840955"
}

@ARTICLE{Quan2011-px,
  title    = "High-density localization of active molecules using Structured
              Sparse Model and Bayesian Information Criterion",
  author   = "Quan, Tingwei and Zhu, Hongyu and Liu, Xiaomao and Liu, Yongfeng
              and Ding, Jiuping and Zeng, Shaoqun and Huang, Zhen-Li",
  abstract = "Localization-based super-resolution microscopy (or called
              localization microscopy) rely on repeated imaging and
              localization of active molecules, and the spatial resolution
              enhancement of localization microscopy is built upon the
              sacrifice of its temporal resolution. Developing algorithms for
              high-density localization of active molecules is a promising
              approach to increase the speed of localization microscopy. Here
              we present a new algorithm called SSM\_BIC for such purpose. The
              SSM\_BIC combines the advantages of the Structured Sparse Model
              (SSM) and the Bayesian Information Criterion (BIC). Through
              simulation and experimental studies, we evaluate systematically
              the performance between the SSM\_BIC and the conventional Sparse
              algorithm in high-density localization of active molecules. We
              show that the SSM\_BIC is superior in processing single molecule
              images with weak signal embedded in strong background.",
  journal  = "Opt. Express",
  volume   =  19,
  number   =  18,
  pages    = "16963--16974",
  month    =  aug,
  year     =  2011,
  language = "en",
  issn     = "1094-4087",
  pmid     = "21935056",
  doi      = "10.1364/OE.19.016963"
}

@ARTICLE{Kubitscheck2000-gt,
  title    = "Imaging and tracking of single {GFP} molecules in solution",
  author   = "Kubitscheck, U and K{\"u}ckmann, O and Kues, T and Peters, R",
  abstract = "Visualization and tracking of single fluorescent molecules is a
              recent development in optical microscopy holding great promise
              for the study of cell biological processes. However, all
              experimental strategies realized so far confined the observation
              to extremely thin interfacial layers. The detection and
              characterization of single molecules in three-dimensionally
              extended systems such as living cells has yet to be accomplished.
              We show, here, for the first time that single protein molecules
              can be visualized and tracked in three-dimensional (3D) samples
              at room temperature. Using a wide-field fluorescence microscope
              equipped with an Ar(+)-laser and a low-light-level CCD camera,
              single molecules of the green fluorescent protein (GFP) were
              detected in gels and viscous solutions at depths of up to
              approximately 10 microm from the interface. A time resolution of
              5 ms was achieved by a high-speed framing mode. The
              two-dimensional localization accuracy was determined to be
              approximately 30 nm. The number of photons emitted by single GFP
              molecules before photodestruction was found to be < or = 4 *
              10(5). Freely diffusing GFP molecules could be tracked over up to
              nine images acquired at a frame rate of approximately 80 Hz. From
              the trajectories, the diffusion coefficients of single GFP
              molecules were derived and found to agree well with expectation
              and microphotolysis measurements. Our results imply that the
              visualization and tracking of single molecules in living cells is
              possible.",
  journal  = "Biophys. J.",
  volume   =  78,
  number   =  4,
  pages    = "2170--2179",
  month    =  apr,
  year     =  2000,
  language = "en",
  issn     = "0006-3495",
  pmid     = "10733995",
  doi      = "10.1016/S0006-3495(00)76764-6",
  pmc      = "PMC1300809"
}

@ARTICLE{Rosen2020-zn,
  title    = "Dynamics of {RNA} polymerase {II} and elongation factor Spt4/5
              recruitment during activator-dependent transcription",
  author   = "Rosen, Grace A and Baek, Inwha and Friedman, Larry J and Joo, Yoo
              Jin and Buratowski, Stephen and Gelles, Jeff",
  abstract = "In eukaryotes, RNA polymerase II (RNApII) transcribes messenger
              RNA from template DNA. Decades of experiments have identified the
              proteins needed for transcription activation, initiation complex
              assembly, and productive elongation. However, the dynamics of
              recruitment of these proteins to transcription complexes, and of
              the transitions between these steps, are poorly understood. We
              used multiwavelength single-molecule fluorescence microscopy to
              directly image and quantitate these dynamics in a budding yeast
              nuclear extract that reconstitutes activator-dependent
              transcription in vitro. A strong activator (Gal4-VP16) greatly
              stimulated reversible binding of individual RNApII molecules to
              template DNA. Binding of labeled elongation factor Spt4/5 to DNA
              typically followed RNApII binding, was NTP dependent, and was
              correlated with association of mRNA binding protein Hek2,
              demonstrating specificity of Spt4/5 binding to elongation
              complexes. Quantitative kinetic modeling shows that only a
              fraction of RNApII binding events are productive and implies a
              rate-limiting step, probably associated with recruitment of
              general transcription factors, needed to assemble a
              transcription-competent preinitiation complex at the promoter.
              Spt4/5 association with transcription complexes was slowly
              reversible, with DNA-bound RNApII molecules sometimes binding and
              releasing Spt4/5 multiple times. The average Spt4/5 residence
              time was of similar magnitude to the time required to transcribe
              an average length yeast gene. These dynamics suggest that a
              single Spt4/5 molecule remains associated during a typical
              transcription event, yet can dissociate from RNApII to allow
              disassembly of abnormally long-lived (i.e., stalled) elongation
              complexes.",
  journal  = "Proc. Natl. Acad. Sci. U. S. A.",
  volume   =  117,
  number   =  51,
  pages    = "32348--32357",
  month    =  dec,
  year     =  2020,
  language = "en",
  issn     = "0027-8424, 1091-6490",
  pmid     = "33293419",
  doi      = "10.1073/pnas.2011224117",
  pmc      = "PMC7768755"
}

@ARTICLE{Hoskins2011-md,
  title    = "Ordered and dynamic assembly of single spliceosomes",
  author   = "Hoskins, Aaron A and Friedman, Larry J and Gallagher, Sarah S and
              Crawford, Daniel J and Anderson, Eric G and Wombacher, Richard
              and Ramirez, Nicholas and Cornish, Virginia W and Gelles, Jeff
              and Moore, Melissa J",
  abstract = "The spliceosome is the complex macromolecular machine responsible
              for removing introns from precursors to messenger RNAs
              (pre-mRNAs). We combined yeast genetic engineering, chemical
              biology, and multiwavelength fluorescence microscopy to follow
              assembly of single spliceosomes in real time in whole-cell
              extracts. We find that individual spliceosomal subcomplexes
              associate with pre-mRNA sequentially via an ordered pathway to
              yield functional spliceosomes and that association of every
              subcomplex is reversible. Further, early subcomplex binding
              events do not fully commit a pre-mRNA to splicing; rather,
              commitment increases as assembly proceeds. These findings have
              important implications for the regulation of alternative
              splicing. This experimental strategy should prove widely useful
              for mechanistic analysis of other macromolecular machines in
              environments approaching the complexity of living cells.",
  journal  = "Science",
  volume   =  331,
  number   =  6022,
  pages    = "1289--1295",
  month    =  mar,
  year     =  2011,
  language = "en",
  issn     = "0036-8075, 1095-9203",
  pmid     = "21393538",
  doi      = "10.1126/science.1198830",
  pmc      = "PMC3086749"
}

@ARTICLE{Van_de_Meent2018-mi,
  title         = "An Introduction to Probabilistic Programming",
  author        = "van de Meent, Jan-Willem and Paige, Brooks and Yang,
                   Hongseok and Wood, Frank",
  abstract      = "This document is designed to be a first-year graduate-level
                   introduction to probabilistic programming. It not only
                   provides a thorough background for anyone wishing to use a
                   probabilistic programming system, but also introduces the
                   techniques needed to design and build these systems. It is
                   aimed at people who have an undergraduate-level
                   understanding of either or, ideally, both probabilistic
                   machine learning and programming languages. We start with a
                   discussion of model-based reasoning and explain why
                   conditioning as a foundational computation is central to the
                   fields of probabilistic machine learning and artificial
                   intelligence. We then introduce a simple first-order
                   probabilistic programming language (PPL) whose programs
                   define static-computation-graph, finite-variable-cardinality
                   models. In the context of this restricted PPL we introduce
                   fundamental inference algorithms and describe how they can
                   be implemented in the context of models denoted by
                   probabilistic programs. In the second part of this document,
                   we introduce a higher-order probabilistic programming
                   language, with a functionality analogous to that of
                   established programming languages. This affords the
                   opportunity to define models with dynamic computation
                   graphs, at the cost of requiring inference methods that
                   generate samples by repeatedly executing the program.
                   Foundational inference algorithms for this kind of
                   probabilistic programming language are explained in the
                   context of an interface between program executions and an
                   inference controller. This document closes with a chapter on
                   advanced topics which we believe to be, at the time of
                   writing, interesting directions for probabilistic
                   programming research; directions that point towards a tight
                   integration with deep neural network research and the
                   development of systems for next-generation artificial
                   intelligence applications.",
  month         =  sep,
  year          =  2018,
  url           = "http://arxiv.org/abs/1809.10756",
  journal       = "arXiv",
  eprint        = "1809.10756",
  primaryClass  = "stat.ML",
  arxivid       = "1809.10756"
}

@ARTICLE{Sarkka2019-jw,
  title         = "Temporal Parallelization of Bayesian Smoothers",
  author        = "S{\"a}rkk{\"a}, Simo and Garc{\'\i}a-Fern{\'a}ndez,
                   {\'A}ngel F",
  abstract      = "This paper presents algorithms for temporal parallelization
                   of Bayesian smoothers. We define the elements and the
                   operators to pose these problems as the solutions to
                   all-prefix-sums operations for which efficient parallel
                   scan-algorithms are available. We present the temporal
                   parallelization of the general Bayesian filtering and
                   smoothing equations and specialize them to linear/Gaussian
                   models. The advantage of the proposed algorithms is that
                   they reduce the linear complexity of standard smoothing
                   algorithms with respect to time to logarithmic.",
  month         =  may,
  year          =  2019,
  url           = "http://arxiv.org/abs/1905.13002",
  journal       = "arXiv",
  eprint        = "1905.13002",
  primaryClass  = "stat.CO",
  arxivid       = "1905.13002"
}

@ARTICLE{Sgouralis2019-rt,
  title    = "A Bayesian Nonparametric Approach to Single Molecule F{\"o}rster
              Resonance Energy Transfer",
  author   = "Sgouralis, Ioannis and Madaan, Shreya and Djutanta, Franky and
              Kha, Rachael and Hariadi, Rizal F and Press{\'e}, Steve",
  abstract = "We develop a Bayesian nonparametric framework to analyze single
              molecule FRET (smFRET) data. This framework, a variation on
              infinite hidden Markov models, goes beyond traditional hidden
              Markov analysis, which already treats photon shot noise, in three
              critical ways: (1) it learns the number of molecular states
              present in a smFRET time trace (a hallmark of nonparametric
              approaches), (2) it accounts, simultaneously and
              self-consistently, for photophysical features of donor and
              acceptor fluorophores (blinking kinetics, spectral cross-talk,
              detector quantum efficiency), and (3) it treats background
              photons. Point 2 is essential in reducing the tendency of
              nonparametric approaches to overinterpret noisy single molecule
              time traces and so to estimate states and transition kinetics
              robust to photophysical artifacts. As a result, with the proposed
              framework, we obtain accurate estimates of single molecule
              properties even when the supplied traces are excessively noisy,
              subject to photoartifacts, and of short duration. We validate our
              method using synthetic data sets and demonstrate its
              applicability to real data sets from single molecule experiments
              on Holliday junctions labeled with conventional fluorescent dyes.",
  journal  = "J. Phys. Chem. B",
  volume   =  123,
  number   =  3,
  pages    = "675--688",
  month    =  jan,
  year     =  2019,
  language = "en",
  issn     = "1520-6106",
  pmid     = "30571128",
  doi      = "10.1021/acs.jpcb.8b09752",
  pmc      = "PMC6821439"
}

@ARTICLE{Roy2008-fo,
  title     = "A practical guide to single-molecule {FRET}",
  author    = "Roy, Rahul and Hohng, Sungchul and Ha, Taekjip",
  abstract  = "Single-molecule fluorescence resonance energy transfer (smFRET)
               is one of the most general and adaptable single-molecule
               techniques. Despite the explosive growth in the application of
               smFRET to answer biological questions in the last decade, the
               technique has been practiced mostly by biophysicists. We provide
               a practical guide to using smFRET, focusing on the study of
               immobilized molecules that allow measurements of single-molecule
               reaction trajectories from 1 ms to many minutes. We discuss
               issues a biologist must consider to conduct successful smFRET
               experiments, including experimental design, sample preparation,
               single-molecule detection and data analysis. We also describe
               how a smFRET-capable instrument can be built at a reasonable
               cost with off-the-shelf components and operated reliably using
               well-established protocols and freely available software.",
  journal   = "Nat. Methods",
  publisher = "nature.com",
  volume    =  5,
  number    =  6,
  pages     = "507--516",
  month     =  jun,
  year      =  2008,
  language  = "en",
  issn      = "1548-7091, 1548-7105",
  pmid      = "18511918",
  doi       = "10.1038/nmeth.1208",
  pmc       = "PMC3769523"
}

@ARTICLE{Zhang2007-rb,
  title    = "Gaussian approximations of fluorescence microscope point-spread
              function models",
  author   = "Zhang, Bo and Zerubia, Josiane and Olivo-Marin, Jean-Christophe",
  abstract = "We comprehensively study the least-squares Gaussian
              approximations of the diffraction-limited 2D-3D
              paraxial-nonparaxial point-spread functions (PSFs) of the wide
              field fluorescence microscope (WFFM), the laser scanning confocal
              microscope (LSCM), and the disk scanning confocal microscope
              (DSCM). The PSFs are expressed using the Debye integral. Under an
              L(infinity) constraint imposing peak matching, optimal and
              near-optimal Gaussian parameters are derived for the PSFs. With
              an L1 constraint imposing energy conservation, an optimal
              Gaussian parameter is derived for the 2D paraxial WFFM PSF. We
              found that (1) the 2D approximations are all very accurate; (2)
              no accurate Gaussian approximation exists for 3D WFFM PSFs; and
              (3) with typical pinhole sizes, the 3D approximations are
              accurate for the DSCM and nearly perfect for the LSCM. All the
              Gaussian parameters derived in this study are in explicit
              analytical form, allowing their direct use in practical
              applications.",
  journal  = "Appl. Opt.",
  volume   =  46,
  number   =  10,
  pages    = "1819--1829",
  month    =  apr,
  year     =  2007,
  language = "en",
  issn     = "0003-6935",
  pmid     = "17356626",
  doi      = "10.1364/ao.46.001819"
}

% The entry below contains non-ASCII chars that could not be converted
% to a LaTeX equivalent.
@ARTICLE{Zhang2015-xn,
  title    = "Ultrahigh-throughput single-molecule spectroscopy and spectrally
              resolved super-resolution microscopy",
  author   = "Zhang, Zhengyang and Kenny, Samuel J and Hauser, Margaret and Li,
              Wan and Xu, Ke",
  abstract = "By developing a wide-field scheme for spectral measurement and
              implementing photoswitching, we synchronously obtained the
              fluorescence spectra and positions of ∼10(6) single molecules in
              labeled cells in minutes, which consequently enabled spectrally
              resolved, 'true-color' super-resolution microscopy. The method,
              called spectrally resolved stochastic optical reconstruction
              microscopy (SR-STORM), achieved cross-talk-free three-dimensional
              (3D) imaging for four dyes 10 nm apart in emission spectrum.
              Excellent resolution was obtained for every channel, and 3D
              localizations of all molecules were automatically aligned within
              one imaging path.",
  journal  = "Nat. Methods",
  volume   =  12,
  number   =  10,
  pages    = "935--938",
  month    =  oct,
  year     =  2015,
  language = "en",
  issn     = "1548-7091, 1548-7105",
  pmid     = "26280329",
  doi      = "10.1038/nmeth.3528"
}

@ARTICLE{Chistol2015-sc,
  title    = "{Single-Molecule} Visualization of {MCM2-7} {DNA} Loading: Seeing
              Is Believing",
  author   = "Chistol, Gheorghe and Walter, Johannes C",
  abstract = "The first event in the initiation of eukaryotic DNA replication
              is the recruitment of the MCM2-7 ATPase, the core of the
              replicative DNA helicase, to origins. Ticau et al. use
              single-molecule imaging to reveal how ORC, Cdc6, and Cdt1
              cooperate to load MCM2-7 onto DNA, enabling bidirectional
              replication.",
  journal  = "Cell",
  volume   =  161,
  number   =  3,
  pages    = "429--430",
  month    =  apr,
  year     =  2015,
  language = "en",
  issn     = "0092-8674, 1097-4172",
  pmid     = "25910200",
  doi      = "10.1016/j.cell.2015.04.006"
}

@ARTICLE{Perkel2015-vw,
  title    = "{SINGLE} {MOLECULE} {ENZYMOLOGY} {FINDS} {ITS} {STRIDE}",
  author   = "Perkel, Jeffrey",
  abstract = "More techniques aimed at probing the nature of single molecules
              are being developed and advanced in biophysics labs. Jeffrey
              Perkel takes a look at the scientists leading the charge into the
              micro-world.",
  journal  = "Biotechniques",
  volume   =  59,
  number   =  4,
  pages    = "183--4, 186--7",
  month    =  oct,
  year     =  2015,
  language = "en",
  issn     = "0736-6205, 1940-9818",
  pmid     = "26458545",
  doi      = "10.2144/000114337"
}

@ARTICLE{Gourse2012-ke,
  title    = "{CoSMoS} unravels mysteries of transcription initiation",
  author   = "Gourse, Richard L and Landick, Robert",
  abstract = "Using a fluorescence method called colocalization single-molecule
              spectroscopy (CoSMoS), Friedman and Gelles dissect the kinetics
              of transcription initiation at a bacterial promoter. Ultimately,
              CoSMoS could greatly aid the study of the effects of DNA sequence
              and transcription factors on both prokaryotic and eukaryotic
              promoters.",
  journal  = "Cell",
  volume   =  148,
  number   =  4,
  pages    = "635--637",
  month    =  feb,
  year     =  2012,
  language = "en",
  issn     = "0092-8674, 1097-4172",
  pmid     = "22341438",
  doi      = "10.1016/j.cell.2012.01.042",
  pmc      = "PMC3681408"
}

@ARTICLE{Tetone2017-za,
  title    = "Dynamics of {GreB-RNA} polymerase interaction allow a
              proofreading accessory protein to patrol for transcription
              complexes needing rescue",
  author   = "Tetone, Larry E and Friedman, Larry J and Osborne, Melisa L and
              Ravi, Harini and Kyzer, Scotty and Stumper, Sarah K and Mooney,
              Rachel A and Landick, Robert and Gelles, Jeff",
  abstract = "The secondary channel (SC) of multisubunit RNA polymerases
              (RNAPs) allows access to the active site and is a nexus for the
              regulation of transcription. Multiple regulatory proteins bind in
              the SC and reprogram the catalytic activity of RNAP, but the
              dynamics of these factors' interactions with RNAP and how they
              function without cross-interference are unclear. In Escherichia
              coli, GreB is an SC protein that promotes proofreading by
              transcript cleavage in elongation complexes backtracked by
              nucleotide misincorporation. Using multiwavelength
              single-molecule fluorescence microscopy, we observed the dynamics
              of GreB interactions with elongation complexes. GreB binds to
              actively elongating complexes at nearly diffusion-limited rates
              but remains bound for only 0.3-0.5 s, longer than the duration of
              the nucleotide addition cycle but far shorter than the time
              needed to synthesize a complete mRNA. Bound GreB inhibits
              transcript elongation only partially. To test whether GreB
              preferentially binds backtracked complexes, we reconstituted
              complexes stabilized in backtracked and nonbacktracked
              configurations. By verifying the functional state of each
              molecular complex studied, we could exclude models in which GreB
              is selectively recruited to backtracked complexes or is ejected
              from RNAP by catalytic turnover. Instead, GreB binds rapidly and
              randomly to elongation complexes, patrolling for those requiring
              nucleolytic rescue, and its short residence time minimizes RNAP
              inhibition. The results suggest a general mechanism by which SC
              factors may cooperate to regulate RNAP while minimizing mutual
              interference.",
  journal  = "Proc. Natl. Acad. Sci. U. S. A.",
  volume   =  114,
  number   =  7,
  pages    = "E1081--E1090",
  month    =  feb,
  year     =  2017,
  language = "en",
  issn     = "0027-8424, 1091-6490",
  pmid     = "28137878",
  doi      = "10.1073/pnas.1616525114",
  pmc      = "PMC5320998"
}

@ARTICLE{Smith2013-of,
  title    = "Pathway of actin filament branch formation by Arp2/3 complex
              revealed by single-molecule imaging",
  author   = "Smith, Benjamin A and Daugherty-Clarke, Karen and Goode, Bruce L
              and Gelles, Jeff",
  abstract = "Actin filament nucleation by actin-related protein (Arp) 2/3
              complex is a critical process in cell motility and endocytosis,
              yet key aspects of its mechanism are unknown due to a lack of
              real-time observations of Arp2/3 complex through the nucleation
              process. Triggered by the verprolin homology, central, and acidic
              (VCA) region of proteins in the Wiskott-Aldrich syndrome protein
              (WASp) family, Arp2/3 complex produces new (daughter) filaments
              as branches from the sides of preexisting (mother) filaments. We
              visualized individual fluorescently labeled Arp2/3 complexes
              dynamically interacting with and producing branches on growing
              actin filaments in vitro. Branch formation was strikingly
              inefficient, even in the presence of VCA: only ~1\% of
              filament-bound Arp2/3 complexes yielded a daughter filament. VCA
              acted at multiple steps, increasing both the association rate of
              Arp2/3 complexes with mother filament and the fraction of
              filament-bound complexes that nucleated a daughter. The results
              lead to a quantitative kinetic mechanism for branched actin
              assembly, revealing the steps that can be stimulated by
              additional cellular factors.",
  journal  = "Proc. Natl. Acad. Sci. U. S. A.",
  volume   =  110,
  number   =  4,
  pages    = "1285--1290",
  month    =  jan,
  year     =  2013,
  language = "en",
  issn     = "0027-8424, 1091-6490",
  pmid     = "23292935",
  doi      = "10.1073/pnas.1211164110",
  pmc      = "PMC3557048"
}

@ARTICLE{Crawford2008-yx,
  title    = "Visualizing the splicing of single {pre-mRNA} molecules in whole
              cell extract",
  author   = "Crawford, Daniel J and Hoskins, Aaron A and Friedman, Larry J and
              Gelles, Jeff and Moore, Melissa J",
  abstract = "The excision of introns from nascent eukaryotic transcripts is
              catalyzed by the spliceosome, a highly complex and dynamic
              macromolecular machine composed of RNA and protein. Because of
              its complexity, biochemical analysis of the spliceosome has been
              previously limited to bulk assays in largely unfractionated cell
              extracts. We now report development of methodologies for studying
              the splicing of isolated single pre-mRNA molecules in real time.
              In this system, a fluorescently tagged pre-mRNA is tethered to a
              glass surface via its 3'-end. Splicing can be observed in
              Saccharomyces cerevisiae whole cell extract by monitoring loss of
              intron-specific fluorescence with a multi-wavelength total
              internal reflection fluorescence (TIRF) microscope. To prolong
              fluorophore lifetime, two enzyme-based O2 scavenging systems
              compatible with splicing were also developed. This work provides
              a powerful new approach for elucidating the mechanisms of
              spliceosome function and demonstrates the feasibility of
              utilizing TIRF microscopy for biochemical studies of single
              molecules in highly complex environments.",
  journal  = "RNA",
  volume   =  14,
  number   =  1,
  pages    = "170--179",
  month    =  jan,
  year     =  2008,
  language = "en",
  issn     = "1355-8382, 1469-9001",
  pmid     = "18025254",
  doi      = "10.1261/rna.794808",
  pmc      = "PMC2151038"
}

@ARTICLE{Smith2014-rh,
  title    = "Single-molecule studies of actin assembly and disassembly factors",
  author   = "Smith, Benjamin A and Gelles, Jeff and Goode, Bruce L",
  abstract = "The actin cytoskeleton is very dynamic and highly regulated by
              multiple associated proteins in vivo. Understanding how this
              system of proteins functions in the processes of actin network
              assembly and disassembly requires methods to dissect the
              mechanisms of activity of individual factors and of multiple
              factors acting in concert. The advent of single-filament and
              single-molecule fluorescence imaging methods has provided a
              powerful new approach to discovering actin-regulatory activities
              and obtaining direct, quantitative insights into the pathways of
              molecular interactions that regulate actin network architecture
              and dynamics. Here we describe techniques for acquisition and
              analysis of single-molecule data, applied to the novel challenges
              of studying the filament assembly and disassembly activities of
              actin-associated proteins in vitro. We discuss the advantages of
              single-molecule analysis in directly visualizing the order of
              molecular events, measuring the kinetic rates of filament binding
              and dissociation, and studying the coordination among multiple
              factors. The methods described here complement traditional
              biochemical approaches in elucidating actin-regulatory mechanisms
              in reconstituted filamentous networks.",
  journal  = "Methods Enzymol.",
  volume   =  540,
  pages    = "95--117",
  year     =  2014,
  language = "en",
  issn     = "0076-6879, 1557-7988",
  pmid     = "24630103",
  doi      = "10.1016/B978-0-12-397924-7.00006-6",
  pmc      = "PMC4037564"
}

@ARTICLE{Hellen1987-we,
  title     = "Fluorescence emission at dielectric and metal-film interfaces",
  author    = "Hellen, Edward H and Axelrod, Daniel",
  abstract  = "It is well known that the classical optical properties of a bare
               or metal-film-coated dielectric surface significantly the
               emission pattern of a fluorophore in close proximity to it. Most
               previous classical calculations of this perturb model the
               fluorophore as a continuous fixed-amplitude dipole acting as a
               simple radiator. However, for effect modeling steady-state
               excitation, a fixed-power dipole is more appropriate. This
               modification corresponds to normalizing fixed-amplitude dipole
               intensities by the total dissipated power, which is itself
               dependent on fluorophore orientation and proximity to the
               surface. The results for the fixed-power model differ
               nontrivially from the fixed-amplitude model. Using the
               fixed-power dipole model, we calculate the
               observation-angle-dependent intensity as a function of the
               fluorophore's orientation and distance from the surface. The
               surface can have an intermediate layer of arbitrary thickness on
               it, which is used to model a metal-film-coated dielectric. In
               addition, general expressions are derived for the emission power
               as observed through a circular-aperture collection system (such
               as a microscope objective) located on either side of the
               interface. These expressions are applied to several common cases
               of fluorophore spatial and orientational distributions at bare
               glass--water and metal-film-coated glass-water interfaces. The
               results suggest practical experimental approaches for measuring
               the spatial and orientational distribution of fluorophores
               adsorbed at a surface, utilizing the distance-dependent
               fluorescence near a metalized surface and optimizing the
               collection efficiency from a well-defined volume near a
               quenching surface.",
  journal   = "J. Opt. Soc. Am. B, JOSAB",
  publisher = "Optical Society of America",
  volume    =  4,
  number    =  3,
  pages     = "337--350",
  month     =  mar,
  year      =  1987,
  language  = "en",
  issn      = "1520-8540",
  doi       = "10.1364/JOSAB.4.000337"
}

@ARTICLE{Larson2014-os,
  title    = "Design and construction of a multiwavelength, micromirror total
              internal reflectance fluorescence microscope",
  author   = "Larson, Joshua and Kirk, Matt and Drier, Eric A and O'Brien,
              William and MacKay, James F and Friedman, Larry J and Hoskins,
              Aaron A",
  abstract = "Colocalization single-molecule spectroscopy (CoSMoS) has proven
              to be a useful method for studying the composition, kinetics and
              mechanisms of complex cellular machines. Key to the technique is
              the ability to simultaneously monitor multiple proteins and/or
              nucleic acids as they interact with one another. Here we describe
              a protocol for constructing a CoSMoS micromirror total internal
              reflection fluorescence microscope (mmTIRFM). Design and
              construction of a scientific microscope often requires a number
              of custom components and a substantial time commitment. In our
              protocol, we have streamlined this process by implementation of a
              commercially available microscopy platform designed to
              accommodate the optical components necessary for an mmTIRFM. The
              mmTIRF system eliminates the need for machining custom parts by
              the end user and facilitates optical alignment. Depending on the
              experience level of the microscope builder, these time savings
              and the following protocol can enable mmTIRF construction to be
              completed within 2 months.",
  journal  = "Nat. Protoc.",
  volume   =  9,
  number   =  10,
  pages    = "2317--2328",
  month    =  oct,
  year     =  2014,
  language = "en",
  issn     = "1754-2189",
  pmid     = "25188633",
  doi      = "10.1038/nprot.2014.155",
  pmc      = "PMC4648537"
}

@ARTICLE{Rubin-Delanchy2015-qg,
  title    = "Bayesian cluster identification in single-molecule localization
              microscopy data",
  author   = "Rubin-Delanchy, Patrick and Burn, Garth L and Griffi{\'e},
              Juliette and Williamson, David J and Heard, Nicholas A and Cope,
              Andrew P and Owen, Dylan M",
  abstract = "Single-molecule localization-based super-resolution microscopy
              techniques such as photoactivated localization microscopy (PALM)
              and stochastic optical reconstruction microscopy (STORM) produce
              pointillist data sets of molecular coordinates. Although many
              algorithms exist for the identification and localization of
              molecules from raw image data, methods for analyzing the
              resulting point patterns for properties such as clustering have
              remained relatively under-studied. Here we present a model-based
              Bayesian approach to evaluate molecular cluster assignment
              proposals, generated in this study by analysis based on Ripley's
              K function. The method takes full account of the individual
              localization precisions calculated for each emitter. We validate
              the approach using simulated data, as well as experimental data
              on the clustering behavior of CD3$\zeta$, a subunit of the CD3 T
              cell receptor complex, in resting and activated primary human T
              cells.",
  journal  = "Nat. Methods",
  volume   =  12,
  number   =  11,
  pages    = "1072--1076",
  month    =  nov,
  year     =  2015,
  language = "en",
  issn     = "1548-7091, 1548-7105",
  pmid     = "26436479",
  doi      = "10.1038/nmeth.3612"
}

@ARTICLE{Hocine2013-ux,
  title    = "Single-molecule analysis of gene expression using two-color {RNA}
              labeling in live yeast",
  author   = "Hocine, Sami and Raymond, Pascal and Zenklusen, Daniel and Chao,
              Jeffrey A and Singer, Robert H",
  abstract = "Live-cell imaging of mRNA yields important insights into gene
              expression, but it has generally been limited to the labeling of
              one RNA species and has never been used to count single mRNAs
              over time in yeast. We demonstrate a two-color imaging system
              with single-molecule resolution using MS2 and PP7 RNA labeling.
              We use this methodology to measure intrinsic noise in mRNA levels
              and RNA polymerase II kinetics at a single gene.",
  journal  = "Nat. Methods",
  volume   =  10,
  number   =  2,
  pages    = "119--121",
  month    =  feb,
  year     =  2013,
  language = "en",
  issn     = "1548-7091, 1548-7105",
  pmid     = "23263691",
  doi      = "10.1038/nmeth.2305",
  pmc      = "PMC3899799"
}

@ARTICLE{Larson2013-ud,
  title    = "Direct observation of frequency modulated transcription in single
              cells using light activation",
  author   = "Larson, Daniel R and Fritzsch, Christoph and Sun, Liang and Meng,
              Xiuhau and Lawrence, David S and Singer, Robert H",
  abstract = "Single-cell analysis has revealed that transcription is dynamic
              and stochastic, but tools are lacking that can determine the
              mechanism operating at a single gene. Here we utilize
              single-molecule observations of RNA in fixed and living cells to
              develop a single-cell model of steroid-receptor mediated gene
              activation. We determine that steroids drive mRNA synthesis by
              frequency modulation of transcription. This digital behavior in
              single cells gives rise to the well-known analog dose response
              across the population. To test this model, we developed a
              light-activation technology to turn on a single
              steroid-responsive gene and follow dynamic synthesis of RNA from
              the activated locus.
              DOI:http://dx.doi.org/10.7554/eLife.00750.001.",
  journal  = "Elife",
  volume   =  2,
  pages    = "e00750",
  month    =  sep,
  year     =  2013,
  language = "en",
  issn     = "2050-084X",
  pmid     = "24069527",
  doi      = "10.7554/eLife.00750",
  pmc      = "PMC3780543"
}

@ARTICLE{Manley2008-bw,
  title    = "High-density mapping of single-molecule trajectories with
              photoactivated localization microscopy",
  author   = "Manley, Suliana and Gillette, Jennifer M and Patterson, George H
              and Shroff, Hari and Hess, Harald F and Betzig, Eric and
              Lippincott-Schwartz, Jennifer",
  abstract = "We combined photoactivated localization microscopy (PALM) with
              live-cell single-particle tracking to create a new method termed
              sptPALM. We created spatially resolved maps of single-molecule
              motions by imaging the membrane proteins Gag and VSVG, and
              obtained several orders of magnitude more trajectories per cell
              than traditional single-particle tracking enables. By probing
              distinct subsets of molecules, sptPALM can provide insight into
              the origins of spatial and temporal heterogeneities in membranes.",
  journal  = "Nat. Methods",
  volume   =  5,
  number   =  2,
  pages    = "155--157",
  month    =  feb,
  year     =  2008,
  language = "en",
  issn     = "1548-7091, 1548-7105",
  pmid     = "18193054",
  doi      = "10.1038/nmeth.1176"
}

@ARTICLE{Manley2010-le,
  title    = "Single-particle tracking photoactivated localization microscopy
              for mapping single-molecule dynamics",
  author   = "Manley, Suliana and Gillette, Jennifer M and Lippincott-Schwartz,
              Jennifer",
  abstract = "Recent developments in single-molecule localization techniques
              using photoactivatable fluorescent proteins have allowed the
              probing of single-molecule motion in a living cell with high
              specificity, millisecond time resolution, and nanometer spatial
              resolution. Analyzing the dynamics of individual molecules at
              high densities in this manner promises to provide new insights
              into the mechanisms of many biological processes, including
              protein heterogeneity in the plasma membrane, the dynamics of
              cytoskeletal flow, and clustering of receptor complexes in
              response to signaling cues. Here we describe the method of
              single-molecule tracking photoactivated localization microscopy
              (sptPALM) and discuss how its use can contribute to a
              quantitative understanding of fundamental cellular processes.",
  journal  = "Methods Enzymol.",
  volume   =  475,
  pages    = "109--120",
  year     =  2010,
  language = "en",
  issn     = "0076-6879, 1557-7988",
  pmid     = "20627155",
  doi      = "10.1016/S0076-6879(10)75005-9",
  pmc      = "PMC3690942"
}

@ARTICLE{Levene2003-fe,
  title    = "Zero-mode waveguides for single-molecule analysis at high
              concentrations",
  author   = "Levene, M J and Korlach, J and Turner, S W and Foquet, M and
              Craighead, H G and Webb, W W",
  abstract = "Optical approaches for observing the dynamics of single molecules
              have required pico- to nanomolar concentrations of fluorophore in
              order to isolate individual molecules. However, many biologically
              relevant processes occur at micromolar ligand concentrations,
              necessitating a reduction in the conventional observation volume
              by three orders of magnitude. We show that arrays of zero-mode
              waveguides consisting of subwavelength holes in a metal film
              provide a simple and highly parallel means for studying
              single-molecule dynamics at micromolar concentrations with
              microsecond temporal resolution. We present observations of DNA
              polymerase activity as an example of the effectiveness of
              zero-mode waveguides for performing single-molecule experiments
              at high concentrations.",
  journal  = "Science",
  volume   =  299,
  number   =  5607,
  pages    = "682--686",
  month    =  jan,
  year     =  2003,
  language = "en",
  issn     = "0036-8075, 1095-9203",
  pmid     = "12560545",
  doi      = "10.1126/science.1079700"
}

@ARTICLE{Crawford2013-se,
  title    = "Single-molecule colocalization {FRET} evidence that spliceosome
              activation precedes stable approach of 5' splice site and branch
              site",
  author   = "Crawford, Daniel J and Hoskins, Aaron A and Friedman, Larry J and
              Gelles, Jeff and Moore, Melissa J",
  abstract = "Removal of introns from the precursors to messenger RNA
              (pre-mRNAs) requires close apposition of intron ends by the
              spliceosome, but when and how apposition occurs is unclear. We
              investigated the process by which intron ends are brought
              together using single-molecule fluorescence resonance energy
              transfer together with colocalization single-molecule
              spectroscopy, a combination of methods that can directly reveal
              how conformational transitions in macromolecular machines are
              coupled to specific assembly and disassembly events. The FRET
              measurements suggest that the 5' splice site and branch site
              remain physically separated throughout spliceosome assembly, and
              only approach one another after the spliceosome is activated for
              catalysis, at which time the pre-mRNA becomes highly dynamic.
              Separation of the sites of chemistry until very late in the
              splicing pathway may be crucial for preventing splicing at
              incorrect sites.",
  journal  = "Proc. Natl. Acad. Sci. U. S. A.",
  volume   =  110,
  number   =  17,
  pages    = "6783--6788",
  month    =  apr,
  year     =  2013,
  language = "en",
  issn     = "0027-8424, 1091-6490",
  pmid     = "23569281",
  doi      = "10.1073/pnas.1219305110",
  pmc      = "PMC3637735"
}

@ARTICLE{Larson2014-qi,
  title    = "Visualizing cellular machines with colocalization single molecule
              microscopy",
  author   = "Larson, Joshua D and Rodgers, Margaret L and Hoskins, Aaron A",
  abstract = "Many of the cell's macromolecular machines contain multiple
              components that transiently associate with one another. This
              compositional and dynamic complexity presents a challenge for
              understanding how these machines are constructed and function.
              Colocalization single molecule spectroscopy enables simultaneous
              observation of individual components of these machines in
              real-time and grants a unique window into processes that are
              typically obscured in ensemble assays. Colocalization experiments
              can yield valuable information about assembly pathways,
              compositional heterogeneity, and kinetics that together
              contribute to the development of richly detailed reaction
              mechanisms. This review focuses on recent advances in
              colocalization single molecule spectroscopy and how this
              technique has been applied to enhance our understanding of
              transcription, RNA splicing, and translation.",
  journal  = "Chem. Soc. Rev.",
  volume   =  43,
  number   =  4,
  pages    = "1189--1200",
  month    =  feb,
  year     =  2014,
  language = "en",
  issn     = "0306-0012, 1460-4744",
  pmid     = "23970346",
  doi      = "10.1039/c3cs60208g",
  pmc      = "PMC3946777"
}

@ARTICLE{Dulin2013-gg,
  title    = "Studying genomic processes at the single-molecule level:
              introducing the tools and applications",
  author   = "Dulin, David and Lipfert, Jan and Moolman, M Charl and Dekker,
              Nynke H",
  abstract = "To understand genomic processes such as transcription,
              translation or splicing, we need to be able to study their
              spatial and temporal organization at the molecular level.
              Single-molecule approaches provide this opportunity, allowing
              researchers to monitor molecular conformations, interactions or
              diffusion quantitatively and in real time in purified systems and
              in the context of the living cell. This Review introduces the
              types of application of single-molecule approaches that can
              enhance our understanding of genome function.",
  journal  = "Nat. Rev. Genet.",
  volume   =  14,
  number   =  1,
  pages    = "9--22",
  month    =  jan,
  year     =  2013,
  language = "en",
  issn     = "1471-0056, 1471-0064",
  pmid     = "23150038",
  doi      = "10.1038/nrg3316"
}

@ARTICLE{Joo2013-uc,
  title    = "Bringing single-molecule spectroscopy to macromolecular protein
              complexes",
  author   = "Joo, Chirlmin and Fareh, Mohamed and Kim, V Narry",
  abstract = "Single-molecule fluorescence spectroscopy offers real-time,
              nanometer-resolution information. Over the past two decades, this
              emerging single-molecule technique has been rapidly adopted to
              investigate the structural dynamics and biological functions of
              proteins. Despite this remarkable achievement, single-molecule
              fluorescence techniques must be extended to macromolecular
              protein complexes that are physiologically more relevant for
              functional studies. In this review, we present recent major
              breakthroughs for investigating protein complexes within cell
              extracts using single-molecule fluorescence. We outline the
              challenges, future prospects and potential applications of these
              new single-molecule fluorescence techniques in biological and
              clinical research.",
  journal  = "Trends Biochem. Sci.",
  volume   =  38,
  number   =  1,
  pages    = "30--37",
  month    =  jan,
  year     =  2013,
  language = "en",
  issn     = "0968-0004",
  pmid     = "23200186",
  doi      = "10.1016/j.tibs.2012.10.005",
  pmc      = "PMC3558732"
}

@ARTICLE{Funatsu1995-wx,
  title    = "Imaging of single fluorescent molecules and individual {ATP}
              turnovers by single myosin molecules in aqueous solution",
  author   = "Funatsu, T and Harada, Y and Tokunaga, M and Saito, K and
              Yanagida, T",
  abstract = "Visualization of single actin filaments by fluorescence
              microscopy led to the development of new in vitro assays for
              analysing actomyosin-based motility at the molecular level. The
              ability to manipulate actin filaments with a microneedle or an
              optical trap combined with position-sensitive detectors has
              enabled direct measurements of nanometre displacements and
              piconewton forces exerted by individual myosin molecules. To
              elucidate how myosin generates movement, it is necessary to
              understand how ATP hydrolysis is coupled to mechanical work at
              the level of the single molecule. But the most sensitive
              microscopic ATPase assay available still requires over 1,000
              myosins. To enhance the sensitivity of such assays, we have
              refined epifluorescence and total internal reflection
              microscopies to visualize single fluorescent dye molecules. We
              report here that this approach can be used directly to image
              single fluorescently labelled myosin molecules and detect
              individual ATP turnover reactions. In contrast to previously
              reported single fluorescent molecule imaging methods, which used
              specimens immobilized on an air-dried surface, our method allows
              video-rate imaging of single molecules in aqueous solution, and
              hence can be applied to the study of many types of enzymes and
              biomolecules.",
  journal  = "Nature",
  volume   =  374,
  number   =  6522,
  pages    = "555--559",
  month    =  apr,
  year     =  1995,
  language = "en",
  issn     = "0028-0836, 1476-4687",
  pmid     = "7700383",
  doi      = "10.1038/374555a0"
}

@ARTICLE{Wong2008-dq,
  title    = "Interconvertible lac {repressor-DNA} loops revealed by
              single-molecule experiments",
  author   = "Wong, Oi Kwan and Guthold, Martin and Erie, Dorothy A and Gelles,
              Jeff",
  abstract = "At many promoters, transcription is regulated by simultaneous
              binding of a protein to multiple sites on DNA, but the structures
              and dynamics of such transcription factor-mediated DNA loops are
              poorly understood. We directly examined in vitro loop formation
              mediated by Escherichia coli lactose repressor using
              single-molecule structural and kinetics methods. Small (
              approximately 150 bp) loops form quickly and stably, even with
              out-of-phase operator spacings. Unexpectedly, repeated
              spontaneous transitions between two distinct loop structures were
              observed in individual protein-DNA complexes. The results imply a
              dynamic equilibrium between a novel loop structure with the
              repressor in its crystallographic ``V'' conformation and a second
              structure with a more extended linear repressor conformation that
              substantially lessens the DNA bending strain. The ability to
              switch between different loop structures may help to explain how
              robust transcription regulation is maintained even though the
              mechanical work required to form a loop may change substantially
              with metabolic conditions.",
  journal  = "PLoS Biol.",
  volume   =  6,
  number   =  9,
  pages    = "e232",
  month    =  sep,
  year     =  2008,
  language = "en",
  issn     = "1544-9173, 1545-7885",
  pmid     = "18828671",
  doi      = "10.1371/journal.pbio.0060232",
  pmc      = "PMC2553838"
}

@ARTICLE{Yoon2008-hu,
  title    = "Bayesian inference for improved single molecule fluorescence
              tracking",
  author   = "Yoon, Ji Won and Bruckbauer, Andreas and Fitzgerald, William J
              and Klenerman, David",
  abstract = "Single molecule tracking is widely used to monitor the change in
              position of lipids and proteins in living cells. In many
              experiments in which molecules are tagged with a single or small
              number of fluorophores, the signal/noise ratio may be limiting,
              the number of molecules is not known, and fluorophore blinking
              and photobleaching can occur. All these factors make accurate
              tracking over long trajectories difficult and hence there is
              still a pressing need to develop better algorithms to extract the
              maximum information from a sequence of fluorescence images. We
              describe here a Bayesian-based inference approach, based on a
              trans-dimensional sequential Monte Carlo method that utilizes
              both the spatial and temporal information present in the image
              sequences. We show, using model data, where the real trajectory
              of the molecule is known, that our method allows accurate
              tracking of molecules over long trajectories even with low
              signal/noise ratio and in the presence of fluorescence blinking
              and photobleaching. The method is then applied to real
              experimental data.",
  journal  = "Biophys. J.",
  volume   =  94,
  number   =  12,
  pages    = "4932--4947",
  month    =  jun,
  year     =  2008,
  language = "en",
  issn     = "0006-3495, 1542-0086",
  pmid     = "18339757",
  doi      = "10.1529/biophysj.107.116285",
  pmc      = "PMC2397372"
}

@ARTICLE{Rolfe2011-wf,
  title    = "Automated multidimensional single molecule fluorescence
              microscopy feature detection and tracking",
  author   = "Rolfe, Daniel J and McLachlan, Charles I and Hirsch, Michael and
              Needham, Sarah R and Tynan, Christopher J and Webb, Stephen E D
              and Martin-Fernandez, Marisa L and Hobson, Michael P",
  abstract = "Characterisation of multi-protein interactions in cellular
              networks can be achieved by optical microscopy using
              multidimensional single molecule fluorescence imaging. Proteins
              of different species, individually labelled with a single
              fluorophore, can be imaged as isolated spots (features) of
              different colour light in different channels, and their diffusive
              behaviour in cells directly measured through time. Challenges in
              data analysis have, however, thus far hindered its application in
              biology. A set of methods for the automated analysis of
              multidimensional single molecule microscopy data from cells is
              presented, incorporating Bayesian segmentation-based feature
              detection, image registration and particle tracking. Single
              molecules of different colours can be simultaneously detected in
              noisy, high background data with an arbitrary number of channels,
              acquired simultaneously or time-multiplexed, and then tracked
              through time. The resulting traces can be further analysed, for
              example to detect intensity steps, count discrete intensity
              levels, measure fluorescence resonance energy transfer (FRET) or
              changes in polarisation. Examples are shown illustrating the use
              of the algorithms in investigations of the epidermal growth
              factor receptor (EGFR) signalling network, a key target for
              cancer therapeutics, and with simulated data.",
  journal  = "Eur. Biophys. J.",
  volume   =  40,
  number   =  10,
  pages    = "1167--1186",
  month    =  oct,
  year     =  2011,
  language = "en",
  issn     = "0175-7571, 1432-1017",
  pmid     = "21928120",
  doi      = "10.1007/s00249-011-0747-7"
}

@ARTICLE{Cox2011-nz,
  title    = "Bayesian localization microscopy reveals nanoscale podosome
              dynamics",
  author   = "Cox, Susan and Rosten, Edward and Monypenny, James and
              Jovanovic-Talisman, Tijana and Burnette, Dylan T and
              Lippincott-Schwartz, Jennifer and Jones, Gareth E and Heintzmann,
              Rainer",
  abstract = "We describe a localization microscopy analysis method that is
              able to extract results in live cells using standard fluorescent
              proteins and xenon arc lamp illumination. Our Bayesian analysis
              of the blinking and bleaching (3B analysis) method models the
              entire dataset simultaneously as being generated by a number of
              fluorophores that may or may not be emitting light at any given
              time. The resulting technique allows many overlapping
              fluorophores in each frame and unifies the analysis of the
              localization from blinking and bleaching events. By modeling the
              entire dataset, we were able to use each reappearance of a
              fluorophore to improve the localization accuracy. The high
              performance of this technique allowed us to reveal the nanoscale
              dynamics of podosome formation and dissociation throughout an
              entire cell with a resolution of 50 nm on a 4-s timescale.",
  journal  = "Nat. Methods",
  volume   =  9,
  number   =  2,
  pages    = "195--200",
  month    =  dec,
  year     =  2011,
  language = "en",
  issn     = "1548-7091, 1548-7105",
  pmid     = "22138825",
  doi      = "10.1038/nmeth.1812",
  pmc      = "PMC3272474"
}

@ARTICLE{Smith2015-gf,
  title    = "Probability-based particle detection that enables threshold-free
              and robust in vivo single-molecule tracking",
  author   = "Smith, Carlas S and Stallinga, Sjoerd and Lidke, Keith A and
              Rieger, Bernd and Grunwald, David",
  abstract = "Single-molecule detection in fluorescence nanoscopy has become a
              powerful tool in cell biology but can present vexing issues in
              image analysis, such as limited signal, unspecific background,
              empirically set thresholds, image filtering, and false-positive
              detection limiting overall detection efficiency. Here we present
              a framework in which expert knowledge and parameter tweaking are
              replaced with a probability-based hypothesis test. Our method
              delivers robust and threshold-free signal detection with a
              defined error estimate and improved detection of weaker signals.
              The probability value has consequences for downstream data
              analysis, such as weighing a series of detections and
              corresponding probabilities, Bayesian propagation of probability,
              or defining metrics in tracking applications. We show that the
              method outperforms all current approaches, yielding a detection
              efficiency of >70\% and a false-positive detection rate of <5\%
              under conditions down to 17 photons/pixel background and 180
              photons/molecule signal, which is beneficial for any kind of
              photon-limited application. Examples include limited brightness
              and photostability, phototoxicity in live-cell single-molecule
              imaging, and use of new labels for nanoscopy. We present
              simulations, experimental data, and tracking of low-signal mRNAs
              in yeast cells.",
  journal  = "Mol. Biol. Cell",
  volume   =  26,
  number   =  22,
  pages    = "4057--4062",
  month    =  nov,
  year     =  2015,
  language = "en",
  issn     = "1059-1524, 1939-4586",
  pmid     = "26424801",
  doi      = "10.1091/mbc.E15-06-0448",
  pmc      = "PMC4710236"
}

@ARTICLE{Grimm2015-ea,
  title    = "A general method to improve fluorophores for live-cell and
              single-molecule microscopy",
  author   = "Grimm, Jonathan B and English, Brian P and Chen, Jiji and
              Slaughter, Joel P and Zhang, Zhengjian and Revyakin, Andrey and
              Patel, Ronak and Macklin, John J and Normanno, Davide and Singer,
              Robert H and Lionnet, Timoth{\'e}e and Lavis, Luke D",
  abstract = "Specific labeling of biomolecules with bright fluorophores is the
              keystone of fluorescence microscopy. Genetically encoded
              self-labeling tag proteins can be coupled to synthetic dyes
              inside living cells, resulting in brighter reporters than
              fluorescent proteins. Intracellular labeling using these
              techniques requires cell-permeable fluorescent ligands, however,
              limiting utility to a small number of classic fluorophores. Here
              we describe a simple structural modification that improves the
              brightness and photostability of dyes while preserving spectral
              properties and cell permeability. Inspired by molecular modeling,
              we replaced the N,N-dimethylamino substituents in
              tetramethylrhodamine with four-membered azetidine rings. This
              addition of two carbon atoms doubles the quantum efficiency and
              improves the photon yield of the dye in applications ranging from
              in vitro single-molecule measurements to super-resolution
              imaging. The novel substitution is generalizable, yielding a
              palette of chemical dyes with improved quantum efficiencies that
              spans the UV and visible range.",
  journal  = "Nat. Methods",
  volume   =  12,
  number   =  3,
  pages    = "244--50, 3 p following 250",
  month    =  mar,
  year     =  2015,
  language = "en",
  issn     = "1548-7091, 1548-7105",
  pmid     = "25599551",
  doi      = "10.1038/nmeth.3256",
  pmc      = "PMC4344395"
}

@ARTICLE{Huang2013-bx,
  title    = "Video-rate nanoscopy using {sCMOS} camera-specific
              single-molecule localization algorithms",
  author   = "Huang, Fang and Hartwich, Tobias M P and Rivera-Molina, Felix E
              and Lin, Yu and Duim, Whitney C and Long, Jane J and Uchil,
              Pradeep D and Myers, Jordan R and Baird, Michelle A and Mothes,
              Walther and Davidson, Michael W and Toomre, Derek and Bewersdorf,
              Joerg",
  abstract = "Newly developed scientific complementary metal-oxide
              semiconductor (sCMOS) cameras have the potential to dramatically
              accelerate data acquisition, enlarge the field of view and
              increase the effective quantum efficiency in single-molecule
              switching nanoscopy. However, sCMOS-intrinsic pixel-dependent
              readout noise substantially lowers the localization precision and
              introduces localization artifacts. We present algorithms that
              overcome these limitations and that provide unbiased, precise
              localization of single molecules at the theoretical limit. Using
              these in combination with a multi-emitter fitting algorithm, we
              demonstrate single-molecule localization super-resolution imaging
              at rates of up to 32 reconstructed images per second in fixed and
              living cells.",
  journal  = "Nat. Methods",
  volume   =  10,
  number   =  7,
  pages    = "653--658",
  month    =  jul,
  year     =  2013,
  language = "en",
  issn     = "1548-7091, 1548-7105",
  pmid     = "23708387",
  doi      = "10.1038/nmeth.2488",
  pmc      = "PMC3696415"
}

@ARTICLE{Breitsprecher2012-mj,
  title    = "Rocket launcher mechanism of collaborative actin assembly defined
              by single-molecule imaging",
  author   = "Breitsprecher, Dennis and Jaiswal, Richa and Bombardier, Jeffrey
              P and Gould, Christopher J and Gelles, Jeff and Goode, Bruce L",
  abstract = "Interacting sets of actin assembly factors work together in
              cells, but the underlying mechanisms have remained obscure. We
              used triple-color single-molecule fluorescence microscopy to
              image the tumor suppressor adenomatous polyposis coli (APC) and
              the formin mDia1 during filament assembly. Complexes consisting
              of APC, mDia1, and actin monomers initiated actin filament
              formation, overcoming inhibition by capping protein and profilin.
              Upon filament polymerization, the complexes separated, with mDia1
              moving processively on growing barbed ends while APC remained at
              the site of nucleation. Thus, the two assembly factors directly
              interact to initiate filament assembly and then separate but
              retain independent associations with either end of the growing
              filament.",
  journal  = "Science",
  volume   =  336,
  number   =  6085,
  pages    = "1164--1168",
  month    =  jun,
  year     =  2012,
  language = "en",
  issn     = "0036-8075, 1095-9203",
  pmid     = "22654058",
  doi      = "10.1126/science.1218062",
  pmc      = "PMC3613992"
}

@ARTICLE{Smith2013-qj,
  title    = "Three-color single molecule imaging shows {WASP} detachment from
              Arp2/3 complex triggers actin filament branch formation",
  author   = "Smith, Benjamin A and Padrick, Shae B and Doolittle, Lynda K and
              Daugherty-Clarke, Karen and Corr{\^e}a, Jr, Ivan R and Xu,
              Ming-Qun and Goode, Bruce L and Rosen, Michael K and Gelles, Jeff",
  abstract = "During cell locomotion and endocytosis, membrane-tethered WASP
              proteins stimulate actin filament nucleation by the Arp2/3
              complex. This process generates highly branched arrays of
              filaments that grow toward the membrane to which they are
              tethered, a conflict that seemingly would restrict filament
              growth. Using three-color single-molecule imaging in vitro we
              revealed how the dynamic associations of Arp2/3 complex with
              mother filament and WASP are temporally coordinated with
              initiation of daughter filament growth. We found that WASP
              proteins dissociated from filament-bound Arp2/3 complex prior to
              new filament growth. Further, mutations that accelerated release
              of WASP from filament-bound Arp2/3 complex proportionally
              accelerated branch formation. These data suggest that while WASP
              promotes formation of pre-nucleation complexes, filament growth
              cannot occur until it is triggered by WASP release. This provides
              a mechanism by which membrane-bound WASP proteins can stimulate
              network growth without restraining it.
              DOI:http://dx.doi.org/10.7554/eLife.01008.001.",
  journal  = "Elife",
  volume   =  2,
  pages    = "e01008",
  month    =  sep,
  year     =  2013,
  language = "en",
  issn     = "2050-084X",
  pmid     = "24015360",
  doi      = "10.7554/eLife.01008",
  pmc      = "PMC3762362"
}

@ARTICLE{Noriega2014-vj,
  title    = "Real-time observation of signal recognition particle binding to
              actively translating ribosomes",
  author   = "Noriega, Thomas R and Chen, Jin and Walter, Peter and Puglisi,
              Joseph D",
  abstract = "The signal recognition particle (SRP) directs translating
              ribosome-nascent chain complexes (RNCs) that display a signal
              sequence to protein translocation channels in target membranes.
              All previous work on the initial step of the targeting reaction,
              when SRP binds to RNCs, used stalled and non-translating RNCs.
              This meant that an important dimension of the co-translational
              process remained unstudied. We apply single-molecule fluorescence
              measurements to observe directly and in real-time E. coli SRP
              binding to actively translating RNCs. We show at physiologically
              relevant SRP concentrations that SRP-RNC association and
              dissociation rates depend on nascent chain length and the
              exposure of a functional signal sequence outside the ribosome.
              Our results resolve a long-standing question: how can a limited,
              sub-stoichiometric pool of cellular SRP effectively distinguish
              RNCs displaying a signal sequence from those that are not? The
              answer is strikingly simple: as originally proposed, SRP only
              stably engages translating RNCs exposing a functional signal
              sequence.",
  journal  = "Elife",
  volume   =  3,
  pages    = "e04418",
  month    =  oct,
  year     =  2014,
  language = "en",
  issn     = "2050-084X",
  pmid     = "25358118",
  doi      = "10.7554/eLife.04418",
  pmc      = "PMC4213662"
}

% The entry below contains non-ASCII chars that could not be converted
% to a LaTeX equivalent.
@ARTICLE{OLeary2013-wo,
  title    = "Dynamic recognition of the {mRNA} cap by Saccharomyces cerevisiae
              {eIF4E}",
  author   = "O'Leary, Se{\'a}n E and Petrov, Alexey and Chen, Jin and Puglisi,
              Joseph D",
  abstract = "Recognition of the mRNA 5' m⁷G(5')ppp(5')N cap is key to
              translation initiation for most eukaryotic mRNAs. The cap is
              bound by the eIF4F complex, consisting of a cap-binding protein
              (eIF4E), a ``scaffold'' protein (eIF4G), and an RNA helicase
              (eIF4A). As a central early step in initiation, regulation of
              eIF4F is crucial for cellular viability. Although the structure
              and function of eIF4E have been defined, a dynamic mechanistic
              picture of its activity at the molecular level in the eIF4F·mRNA
              complex is still unavailable. Here, using single-molecule
              fluorescence, we measured the effects of Saccharomyces cerevisiae
              eIF4F factors, mRNA secondary structure, and the poly(A)-binding
              protein Pab1p on eIF4E-mRNA binding dynamics. Our data provide an
              integrated picture of how eIF4G and mRNA structure modulate
              eIF4E-mRNA interaction, and uncover an eIF4G- and
              poly(A)-independent activity of poly(A)-binding protein that
              prolongs the eIF4E·mRNA complex lifetime.",
  journal  = "Structure",
  volume   =  21,
  number   =  12,
  pages    = "2197--2207",
  month    =  dec,
  year     =  2013,
  language = "en",
  issn     = "0969-2126, 1878-4186",
  pmid     = "24183571",
  doi      = "10.1016/j.str.2013.09.016",
  pmc      = "PMC3878992"
}

@ARTICLE{Tsai2014-mi,
  title    = "The dynamics of {SecM-induced} translational stalling",
  author   = "Tsai, Albert and Kornberg, Guy and Johansson, Magnus and Chen,
              Jin and Puglisi, Joseph D",
  abstract = "SecM is an E. coli secretion monitor capable of stalling
              translation on the prokaryotic ribosome without cofactors.
              Biochemical and structural studies have demonstrated that the
              SecM nascent chain interacts with the 50S subunit exit tunnel to
              inhibit peptide bond formation. However, the timescales and
              pathways of stalling on an mRNA remain undefined. To provide a
              dynamic mechanism for stalling, we directly tracked the dynamics
              of elongation on ribosomes translating the SecM stall sequence
              (FSTPVWISQAQGIRAGP) using single-molecule fluorescence
              techniques. Within 1 min, three peptide-ribosome interactions
              work cooperatively over the last five codons of the SecM
              sequence, leading to severely impaired elongation rates beginning
              from the terminal proline and lasting four codons. Our results
              suggest that stalling is tightly linked to the dynamics of
              elongation and underscore the roles that the exit tunnel and
              nascent chain play in controlling fundamental steps in
              translation.",
  journal  = "Cell Rep.",
  volume   =  7,
  number   =  5,
  pages    = "1521--1533",
  month    =  jun,
  year     =  2014,
  language = "en",
  issn     = "2211-1247",
  pmid     = "24836001",
  doi      = "10.1016/j.celrep.2014.04.033",
  pmc      = "PMC4059775"
}

@ARTICLE{Kim2014-zc,
  title    = "Protein-guided {RNA} dynamics during early ribosome assembly",
  author   = "Kim, Hajin and Abeysirigunawarden, Sanjaya C and Chen, Ke and
              Mayerle, Megan and Ragunathan, Kaushik and Luthey-Schulten, Zaida
              and Ha, Taekjip and Woodson, Sarah A",
  abstract = "The assembly of 30S ribosomes requires the precise addition of 20
              proteins to the 16S ribosomal RNA. How early binding proteins
              change the ribosomal RNA structure so that later proteins may
              join the complex is poorly understood. Here we use
              single-molecule fluorescence resonance energy transfer (FRET) to
              observe real-time encounters between Escherichia coli ribosomal
              protein S4 and the 16S 5' domain RNA at an early stage of 30S
              assembly. Dynamic initial S4-RNA complexes pass through a stable
              non-native intermediate before converting to the native complex,
              showing that non-native structures can offer a low free-energy
              path to protein-RNA recognition. Three-colour FRET and molecular
              dynamics simulations reveal how S4 changes the frequency and
              direction of RNA helix motions, guiding a conformational switch
              that enforces the hierarchy of protein addition. These
              protein-guided dynamics offer an alternative explanation for
              induced fit in RNA-protein complexes.",
  journal  = "Nature",
  volume   =  506,
  number   =  7488,
  pages    = "334--338",
  month    =  feb,
  year     =  2014,
  language = "en",
  issn     = "0028-0836, 1476-4687",
  pmid     = "24522531",
  doi      = "10.1038/nature13039",
  pmc      = "PMC3968076"
}

@ARTICLE{Warnasooriya2014-ls,
  title    = "Single-molecule fluorescence-based studies on the dynamics,
              assembly and catalytic mechanism of the spliceosome",
  author   = "Warnasooriya, Chandani and Rueda, David",
  abstract = "Pre-mRNA (precursor mRNA) splicing is a key step in cellular gene
              expression where introns are excised and exons are ligated
              together to produce mature mRNA. This process is catalysed by the
              spliceosome, which consists of five snRNPs (small nuclear
              ribonucleoprotein particles) and numerous protein factors.
              Assembly of these snRNPs and associated proteins is a highly
              dynamic process, making it challenging to study the
              conformational rearrangements and spliceosome assembly kinetics
              in bulk studies. In the present review, we discuss recent studies
              utilizing techniques based on single-molecule detection that have
              helped overcome this challenge. These studies focus on the
              assembly dynamics and splicing kinetics in real-time, which help
              understanding of spliceosomal assembly and catalysis.",
  journal  = "Biochem. Soc. Trans.",
  volume   =  42,
  number   =  4,
  pages    = "1211--1218",
  month    =  aug,
  year     =  2014,
  language = "en",
  issn     = "0300-5127, 1470-8752",
  pmid     = "25110027",
  doi      = "10.1042/BST20140105"
}

@ARTICLE{Krishnan2013-fy,
  title    = "Biased Brownian ratcheting leads to {pre-mRNA} remodeling and
              capture prior to first-step splicing",
  author   = "Krishnan, Ramya and Blanco, Mario R and Kahlscheuer, Matthew L
              and Abelson, John and Guthrie, Christine and Walter, Nils G",
  abstract = "The spliceosome is a dynamic ribonucleoprotein (RNP) machine that
              catalyzes the removal of introns during the two
              transesterification steps of eukaryotic pre-mRNA splicing. Here
              we used single-molecule fluorescence resonance energy transfer to
              monitor the distance of the 5' splice site (5' SS) and branch
              point (BP) of pre-mRNA in affinity-purified spliceosomes stalled
              by a mutation in the DExD/H-box helicase Prp2 immediately before
              the first splicing step. Addition of recombinant Prp2 together
              with NTP and protein cofactor Spp2 rearranges the
              spliceosome-substrate complex to reversibly explore conformations
              with proximal 5' SS and BP that accommodate chemistry. Addition
              of Cwc25, a small heat-stable splicing factor, then strongly
              biases this equilibrium toward the proximal conformation,
              promoting efficient first-step splicing. The spliceosome thus
              functions as a biased Brownian ratchet machine where a helicase
              unlocks thermal fluctuations subsequently rectified by a cofactor
              'pawl', a principle possibly widespread among the many
              helicase-driven RNPs.",
  journal  = "Nat. Struct. Mol. Biol.",
  volume   =  20,
  number   =  12,
  pages    = "1450--1457",
  month    =  dec,
  year     =  2013,
  language = "en",
  issn     = "1545-9993",
  pmid     = "24240612",
  doi      = "10.1038/nsmb.2704",
  pmc      = "PMC3867266"
}

% The entry below contains non-ASCII chars that could not be converted
% to a LaTeX equivalent.
@ARTICLE{Shcherbakova2013-bi,
  title    = "Alternative spliceosome assembly pathways revealed by
              single-molecule fluorescence microscopy",
  author   = "Shcherbakova, Inna and Hoskins, Aaron A and Friedman, Larry J and
              Serebrov, Victor and Corr{\^e}a, Jr, Ivan R and Xu, Ming-Qun and
              Gelles, Jeff and Moore, Melissa J",
  abstract = "Removal of introns from nascent transcripts (pre-mRNAs) by the
              spliceosome is an essential step in eukaryotic gene expression.
              Previous studies have suggested that the earliest steps in
              spliceosome assembly in yeast are highly ordered and the stable
              recruitment of U1 small nuclear ribonucleoprotein particle
              (snRNP) to the 5' splice site necessarily precedes recruitment of
              U2 snRNP to the branch site to form the ``prespliceosome.'' Here,
              using colocalization single-molecule spectroscopy to follow
              initial spliceosome assembly on eight different S. cerevisiae
              pre-mRNAs, we demonstrate that active yeast spliceosomes can form
              by both U1-first and U2-first pathways. Both assembly pathways
              yield prespliceosomes functionally equivalent for subsequent
              U5·U4/U6 tri-snRNP recruitment and for intron excision. Although
              fractional flux through the two pathways varies on different
              introns, both are operational on all introns studied. Thus,
              multiple pathways exist for assembling functional spliceosomes.
              These observations provide insight into the mechanisms of
              cross-intron coordination of initial spliceosome assembly.",
  journal  = "Cell Rep.",
  volume   =  5,
  number   =  1,
  pages    = "151--165",
  month    =  oct,
  year     =  2013,
  language = "en",
  issn     = "2211-1247",
  pmid     = "24075986",
  doi      = "10.1016/j.celrep.2013.08.026",
  pmc      = "PMC3927372"
}

@ARTICLE{Salomon2015-kq,
  title    = "{Single-Molecule} Imaging Reveals that Argonaute Reshapes the
              Binding Properties of Its Nucleic Acid Guides",
  author   = "Salomon, William E and Jolly, Samson M and Moore, Melissa J and
              Zamore, Phillip D and Serebrov, Victor",
  abstract = "Argonaute proteins repress gene expression and defend against
              foreign nucleic acids using short RNAs or DNAs to specify the
              correct target RNA or DNA sequence. We have developed
              single-molecule methods to analyze target binding and cleavage
              mediated by the Argonaute:guide complex, RISC. We find that both
              eukaryotic and prokaryotic Argonaute proteins reshape the
              fundamental properties of RNA:RNA, RNA:DNA, and DNA:DNA
              hybridization---a small RNA or DNA bound to Argonaute as a guide
              no longer follows the well-established rules by which
              oligonucleotides find, bind, and dissociate from complementary
              nucleic acid sequences. Argonautes distinguish substrates from
              targets with similar complementarity. Mouse AGO2, for example,
              binds tighter to miRNA targets than its RNAi cleavage product,
              even though the cleaved product contains more base pairs. By
              re-writing the rules for nucleic acid hybridization, Argonautes
              allow oligonucleotides to serve as specificity determinants with
              thermodynamic and kinetic properties more typical of RNA-binding
              proteins than of RNA or DNA.",
  journal  = "Cell",
  volume   =  162,
  number   =  1,
  pages    = "84--95",
  month    =  jul,
  year     =  2015,
  language = "en",
  issn     = "0092-8674, 1097-4172",
  pmid     = "26140592",
  doi      = "10.1016/j.cell.2015.06.029",
  pmc      = "PMC4503223"
}

@ARTICLE{Friedman2013-sf,
  title    = "{RNA} polymerase approaches its promoter without long-range
              sliding along {DNA}",
  author   = "Friedman, Larry J and Mumm, Jeffrey P and Gelles, Jeff",
  abstract = "Sequence-specific DNA binding proteins must quickly bind target
              sequences, despite the enormously larger amount of nontarget DNA
              present in cells. RNA polymerases (or associated general
              transcription factors) are hypothesized to reach promoter
              sequences by facilitated diffusion (FD). In FD, a protein first
              binds to nontarget DNA and then reaches the target by a 1D
              sliding search. We tested whether Escherichia coli
              $\sigma$(54)RNA polymerase reaches a promoter by FD using the
              colocalization single-molecule spectroscopy (CoSMoS)
              multiwavelength fluorescence microscopy technique. Experiments
              directly compared the rates of initial polymerase binding to and
              dissociation from promoter and nonpromoter DNAs measured in the
              same sample under identical conditions. Binding to a nonpromoter
              DNA was much slower than binding to a promoter-containing DNA of
              the same length, indicating that the detected nonspecific binding
              events are not on the pathway to promoter binding. Truncating one
              of the DNA segments flanking the promoter to a length as short as
              7 bp or lengthening it to ~3,000 bp did not alter the
              promoter-specific binding rate. These results exclude FD over
              distances corresponding to the length of the promoter or longer
              from playing any significant role in accelerating promoter
              search. Instead, the data support a direct binding mechanism, in
              which $\sigma$(54)RNA polymerase reaches the local vicinity of
              promoters by 3D diffusion through solution, and suggest that
              binding may be accelerated by atypical structural or dynamic
              features of promoter DNA. Direct binding explains how polymerase
              can quickly reach a promoter, despite occupancy of
              promoter-flanking DNA by bound proteins that would impede FD.",
  journal  = "Proc. Natl. Acad. Sci. U. S. A.",
  volume   =  110,
  number   =  24,
  pages    = "9740--9745",
  month    =  jun,
  year     =  2013,
  language = "en",
  issn     = "0027-8424, 1091-6490",
  pmid     = "23720315",
  doi      = "10.1073/pnas.1300221110",
  pmc      = "PMC3683791"
}

@ARTICLE{Friedman2012-if,
  title    = "Mechanism of transcription initiation at an activator-dependent
              promoter defined by single-molecule observation",
  author   = "Friedman, Larry J and Gelles, Jeff",
  abstract = "Understanding the pathway and kinetic mechanisms of transcription
              initiation is essential for quantitative understanding of gene
              regulation, but initiation is a multistep process, the features
              of which can be obscured in bulk analysis. We used a
              multiwavelength single-molecule fluorescence colocalization
              approach, CoSMoS, to define the initiation pathway at an
              activator-dependent bacterial $\sigma$(54) promoter that
              recapitulates characteristic features of eukaryotic promoters
              activated by enhancer binding proteins. The experiments
              kinetically characterize all major steps of the initiation
              process, revealing heretofore unknown features, including
              reversible formation of two closed complexes with greatly
              differing stabilities, multiple attempts for each successful
              formation of an open complex, and efficient release of
              $\sigma$(54) from the polymerase core at the start of transcript
              synthesis. Open complexes are committed to transcription,
              suggesting that regulation likely targets earlier steps in the
              mechanism. CoSMoS is a powerful, generally applicable method to
              elucidate the mechanisms of transcription and other multistep
              biochemical processes.",
  journal  = "Cell",
  volume   =  148,
  number   =  4,
  pages    = "679--689",
  month    =  feb,
  year     =  2012,
  language = "en",
  issn     = "0092-8674, 1097-4172",
  pmid     = "22341441",
  doi      = "10.1016/j.cell.2012.01.018",
  pmc      = "PMC3479156"
}

@ARTICLE{Zhang2012-no,
  title    = "Structural basis of transcription initiation",
  author   = "Zhang, Yu and Feng, Yu and Chatterjee, Sujoy and Tuske, Steve and
              Ho, Mary X and Arnold, Eddy and Ebright, Richard H",
  abstract = "During transcription initiation, RNA polymerase (RNAP) binds and
              unwinds promoter DNA to form an RNAP-promoter open complex. We
              have determined crystal structures at 2.9 and 3.0 {\AA}
              resolution of functional transcription initiation complexes
              comprising Thermus thermophilus RNA polymerase, $\sigma$(A), and
              a promoter DNA fragment corresponding to the transcription bubble
              and downstream double-stranded DNA of the RNAP-promoter open
              complex. The structures show that $\sigma$ recognizes the -10
              element and discriminator element through interactions that
              include the unstacking and insertion into pockets of three DNA
              bases and that RNAP recognizes the -4/+2 region through
              interactions that include the unstacking and insertion into a
              pocket of the +2 base. The structures further show that
              interactions between $\sigma$ and template-strand single-stranded
              DNA (ssDNA) preorganize template-strand ssDNA to engage the RNAP
              active center.",
  journal  = "Science",
  volume   =  338,
  number   =  6110,
  pages    = "1076--1080",
  month    =  nov,
  year     =  2012,
  language = "en",
  issn     = "0036-8075, 1095-9203",
  pmid     = "23086998",
  doi      = "10.1126/science.1227786",
  pmc      = "PMC3593053"
}

@ARTICLE{Geertsema2014-bt,
  title    = "Single-molecule studies of polymerase dynamics and stoichiometry
              at the bacteriophage {T7} replication machinery",
  author   = "Geertsema, Hylkje J and Kulczyk, Arkadiusz W and Richardson,
              Charles C and van Oijen, Antoine M",
  abstract = "Replication of DNA plays a central role in transmitting
              hereditary information from cell to cell. To achieve reliable DNA
              replication, multiple proteins form a stable complex, known as
              the replisome, enabling them to act together in a highly
              coordinated fashion. Over the past decade, the roles of the
              various proteins within the replisome have been determined.
              Although many of their interactions have been characterized, it
              remains poorly understood how replication proteins enter and
              leave the replisome. In this study, we visualize fluorescently
              labeled bacteriophage T7 DNA polymerases within the replisome
              while we simultaneously observe the kinetics of the replication
              process. This combination of observables allows us to monitor
              both the activity and dynamics of individual polymerases during
              coordinated leading- and lagging-strand synthesis. Our data
              suggest that lagging-strand polymerases are exchanged at a
              frequency similar to that of Okazaki fragment synthesis and that
              two or more polymerases are present in the replisome during DNA
              replication. Our studies imply a highly dynamic picture of the
              replisome with lagging-strand DNA polymerases residing at the
              fork for the synthesis of only a few Okazaki fragments. Further,
              new lagging-strand polymerases are readily recruited from a pool
              of polymerases that are proximally bound to the replisome and
              continuously replenished from solution.",
  journal  = "Proc. Natl. Acad. Sci. U. S. A.",
  volume   =  111,
  number   =  11,
  pages    = "4073--4078",
  month    =  mar,
  year     =  2014,
  language = "en",
  issn     = "0027-8424, 1091-6490",
  pmid     = "24591606",
  doi      = "10.1073/pnas.1402010111",
  pmc      = "PMC3964090"
}

% The entry below contains non-ASCII chars that could not be converted
% to a LaTeX equivalent.
@ARTICLE{Wang2015-tt,
  title    = "Ribosomal initiation complex-driven changes in the stability and
              dynamics of initiation factor 2 regulate the fidelity of
              translation initiation",
  author   = "Wang, Jiangning and Caban, Kelvin and Gonzalez, Jr, Ruben L",
  abstract = "Joining of the large, 50S, ribosomal subunit to the small, 30S,
              ribosomal subunit initiation complex (IC) during bacterial
              translation initiation is catalyzed by the initiation factor (IF)
              IF2. Because the rate of subunit joining is coupled to the IF,
              transfer RNA (tRNA), and mRNA codon compositions of the 30S IC,
              the subunit joining reaction functions as a kinetic checkpoint
              that regulates the fidelity of translation initiation. Recent
              structural studies suggest that the conformational dynamics of
              the IF2·tRNA sub-complex forming on the intersubunit surface of
              the 30S IC may play a significant role in the mechanisms that
              couple the rate of subunit joining to the IF, tRNA, and codon
              compositions of the 30S IC. To test this hypothesis, we have
              developed a single-molecule fluorescence resonance energy
              transfer signal between IF2 and tRNA that has enabled us to
              monitor the conformational dynamics of the IF2·tRNA sub-complex
              across a series of 30S ICs. Our results demonstrate that 30S ICs
              undergoing rapid subunit joining display a high affinity for IF2
              and an IF2·tRNA sub-complex that primarily samples a single
              conformation. In contrast, 30S ICs that undergo slower subunit
              joining exhibit a decreased affinity for IF2 and/or a change in
              the conformational dynamics of the IF2·tRNA sub-complex. These
              results strongly suggest that 30S IC-driven changes in the
              stability of IF2 and the conformational dynamics of the IF2·tRNA
              sub-complex regulate the efficiency and fidelity of subunit
              joining during translation initiation.",
  journal  = "J. Mol. Biol.",
  volume   =  427,
  number   =  9,
  pages    = "1819--1834",
  month    =  may,
  year     =  2015,
  language = "en",
  issn     = "0022-2836, 1089-8638",
  pmid     = "25596426",
  doi      = "10.1016/j.jmb.2014.12.025",
  pmc      = "PMC4411560"
}

@ARTICLE{Lu2015-jq,
  title     = "Substrate degradation by the proteasome: a single-molecule
               kinetic analysis",
  author    = "Lu, Ying and Lee, Byung-Hoon and King, Randall W and Finley,
               Daniel and Kirschner, Marc W",
  abstract  = "To address how the configuration of conjugated ubiquitins
               determines the recognition of substrates by the proteasome, we
               analyzed the degradation kinetics of substrates with chemically
               defined ubiquitin configurations. Contrary to the view that a
               tetraubiquitin chain is the minimal signal for efficient
               degradation, we find that distributing the ubiquitins as
               diubiquitin chains provides a more efficient signal. To
               understand how the proteasome actually discriminates among
               ubiquitin configurations, we developed single-molecule assays
               that distinguished intermediate steps of degradation
               kinetically. The level of ubiquitin on a substrate drives
               proteasome-substrate interaction, whereas the chain structure of
               ubiquitin affects translocation into the axial channel on the
               proteasome. Together these two features largely determine the
               susceptibility of substrates for proteasomal degradation.",
  journal   = "Science",
  publisher = "American Association for the Advancement of Science",
  volume    =  348,
  number    =  6231,
  pages     = "1250834",
  month     =  apr,
  year      =  2015,
  language  = "en",
  issn      = "0036-8075, 1095-9203",
  pmid      = "25859050",
  doi       = "10.1126/science.1250834",
  pmc       = "PMC4450770"
}

@ARTICLE{Lu2015-eu,
  title    = "Specificity of the anaphase-promoting complex: a single-molecule
              study",
  author   = "Lu, Ying and Wang, Weiping and Kirschner, Marc W",
  abstract = "Biological processes require specific enzymatic reactions,
              paradoxically involving short recognition sequences. As an
              example, cell-cycle timing depends on a sequence of
              ubiquitylation events mediated by the anaphase-promoting complex
              (APC) based on short redundant motifs. To understand the origin
              of specificity, we designed single-molecule fluorescence assays
              that capture transient ubiquitylation reactions. We find that the
              APC-mediated ubiquitylation involves a highly processive initial
              reaction on the substrate, followed by multiple encounters and
              reactions at a slower rate. The initial ubiquitylation greatly
              enhances the substrate's binding affinity in subsequent
              reactions, by both increasing the on-rate and decreasing the
              off-rate. We postulate that these cycles of positive feedback
              enable high specificity for substrates with short recognition
              motifs in a complex cellular environment.",
  journal  = "Science",
  volume   =  348,
  number   =  6231,
  pages    = "1248737",
  month    =  apr,
  year     =  2015,
  language = "en",
  issn     = "0036-8075, 1095-9203",
  pmid     = "25859049",
  doi      = "10.1126/science.1248737",
  pmc      = "PMC4449139"
}

@ARTICLE{Friedman2006-kb,
  title     = "Viewing dynamic assembly of molecular complexes by
               multi-wavelength single-molecule fluorescence",
  author    = "Friedman, Larry J and Chung, Johnson and Gelles, Jeff",
  abstract  = "Complexes of macromolecules that transiently self-assemble,
               perform a particular function, and then dissociate are a
               recurring theme in biology. Such systems often have a large
               number of possible assembly/disassembly intermediates and
               complex, highly branched reaction pathways. Measuring the
               single-step kinetic parameters in these reactions would help to
               identify the functionally significant pathways. We have
               therefore constructed a novel single-molecule fluorescence
               microscope capable of efficiently detecting the colocalization
               of multiple components in a macromolecular complex when each
               component is labeled using a different color fluorescent dye. In
               this through-objective excitation, total internal reflection
               instrument, the dichroic mirror conventionally used to
               spectrally segregate the excitation and emission pathways was
               replaced with small broadband mirrors. This design spatially
               segregates the excitation and emission pathways and thereby
               permits efficient collection of the spectral range of emitted
               fluorescence when three or more dyes are used. In a test
               experiment with surface-immobilized single-stranded DNA
               molecules, we directly monitored the time course of a
               hybridization reaction with three different oligonucleotides,
               each labeled with a different color dye. The experiment reveals
               which of the possible reaction intermediates were traversed by
               each immobilized molecule, measures the hybridization rate
               constants for each oligonucleotide, and characterizes kinetic
               interdependences of the reaction steps.",
  journal   = "Biophys. J.",
  publisher = "Elsevier",
  volume    =  91,
  number    =  3,
  pages     = "1023--1031",
  month     =  aug,
  year      =  2006,
  language  = "en",
  issn      = "0006-3495",
  pmid      = "16698779",
  doi       = "10.1529/biophysj.106.084004",
  pmc       = "PMC1563747"
}

@ARTICLE{Smith2019-yb,
  title    = "An automated Bayesian pipeline for rapid analysis of
              single-molecule binding data",
  author   = "Smith, Carlas S and Jouravleva, Karina and Huisman, Maximiliaan
              and Jolly, Samson M and Zamore, Phillip D and Grunwald, David",
  abstract = "Single-molecule binding assays enable the study of how molecular
              machines assemble and function. Current algorithms can identify
              and locate individual molecules, but require tedious manual
              validation of each spot. Moreover, no solution for
              high-throughput analysis of single-molecule binding data exists.
              Here, we describe an automated pipeline to analyze
              single-molecule data over a wide range of experimental
              conditions. In addition, our method enables state estimation on
              multivariate Gaussian signals. We validate our approach using
              simulated data, and benchmark the pipeline by measuring the
              binding properties of the well-studied, DNA-guided DNA
              endonuclease, TtAgo, an Argonaute protein from the Eubacterium
              Thermus thermophilus. We also use the pipeline to extend our
              understanding of TtAgo by measuring the protein's binding
              kinetics at physiological temperatures and for target DNAs
              containing multiple, adjacent binding sites.",
  journal  = "Nat. Commun.",
  volume   =  10,
  number   =  1,
  pages    = "272",
  month    =  jan,
  year     =  2019,
  language = "en",
  issn     = "2041-1723",
  pmid     = "30655518",
  doi      = "10.1038/s41467-018-08045-5",
  pmc      = "PMC6336789"
}

@ARTICLE{Quan2011-cg,
  title    = "High-density localization of active molecules using Structured
              Sparse Model and Bayesian Information Criterion",
  author   = "Quan, Tingwei and Zhu, Hongyu and Liu, Xiaomao and Liu, Yongfeng
              and Ding, Jiuping and Zeng, Shaoqun and Huang, Zhen-Li",
  abstract = "Localization-based super-resolution microscopy (or called
              localization microscopy) rely on repeated imaging and
              localization of active molecules, and the spatial resolution
              enhancement of localization microscopy is built upon the
              sacrifice of its temporal resolution. Developing algorithms for
              high-density localization of active molecules is a promising
              approach to increase the speed of localization microscopy. Here
              we present a new algorithm called SSM\_BIC for such purpose. The
              SSM\_BIC combines the advantages of the Structured Sparse Model
              (SSM) and the Bayesian Information Criterion (BIC). Through
              simulation and experimental studies, we evaluate systematically
              the performance between the SSM\_BIC and the conventional Sparse
              algorithm in high-density localization of active molecules. We
              show that the SSM\_BIC is superior in processing single molecule
              images with weak signal embedded in strong background.",
  journal  = "Opt. Express",
  volume   =  19,
  number   =  18,
  pages    = "16963--16974",
  month    =  aug,
  year     =  2011,
  language = "en",
  issn     = "1094-4087",
  pmid     = "21935056",
  doi      = "10.1364/OE.19.016963"
}

@ARTICLE{Peng2018-ge,
  title    = "Breaking the Concentration Barrier for {Single-Molecule}
              Fluorescence Measurements",
  author   = "Peng, Sijia and Wang, Wenjuan and Chen, Chunlai",
  abstract = "Fluorescence-based single-molecule techniques have become widely
              used tools to reveal dynamic processes of biomolecules and
              elucidate their molecular mechanisms. However, the concentration
              upper limit of labeled species that can be used in
              single-molecule fluorescence measurements is at the low nm range,
              which is below the Michaelis constants of many enzymatic
              reactions and physiological concentrations of many biomolecules.
              Such discrepancy limits the application of single-molecule
              fluorescence tools. Several techniques have been developed to
              break the concentration barrier. In this Concept, we focus on
              reviewing fundamental principles of these techniques and wish to
              inspire development of new and better tools to achieve this goal.",
  journal  = "Chemistry",
  volume   =  24,
  number   =  5,
  pages    = "1002--1009",
  month    =  jan,
  year     =  2018,
  language = "en",
  issn     = "0947-6539, 1521-3765",
  pmid     = "29044746",
  doi      = "10.1002/chem.201704065"
}

@ARTICLE{Van_Oijen2011-ig,
  title    = "Single-molecule approaches to characterizing kinetics of
              biomolecular interactions",
  author   = "van Oijen, Antoine M",
  abstract = "Single-molecule fluorescence techniques have emerged as powerful
              tools to study biological processes at the molecular level. This
              review describes the application of these methods to the
              characterization of the kinetics of interaction between
              biomolecules. A large number of single-molecule assays have been
              developed that visualize association and dissociation kinetics in
              vitro by fluorescently labeling binding partners and observing
              their interactions over time. Even though recent progress has
              been significant, there are certain limitations to this approach.
              To allow the observation of individual, fluorescently labeled
              molecules requires low, nanomolar concentrations. I will discuss
              how such concentration requirements in single-molecule
              experiments limit their applicability to investigate
              intermolecular interactions and how recent technical advances
              deal with this issue.",
  journal  = "Curr. Opin. Biotechnol.",
  volume   =  22,
  number   =  1,
  pages    = "75--80",
  month    =  feb,
  year     =  2011,
  language = "en",
  issn     = "0958-1669, 1879-0429",
  pmid     = "21036593",
  doi      = "10.1016/j.copbio.2010.10.002"
}

@ARTICLE{Matthews1975-rw,
  title    = "Comparison of the predicted and observed secondary structure of
              {T4} phage lysozyme",
  author   = "Matthews, B W",
  abstract = "Predictions of the secondary structure of T4 phage lysozyme, made
              by a number of investigators on the basis of the amino acid
              sequence, are compared with the structure of the protein
              determined experimentally by X-ray crystallography. Within the
              amino terminal half of the molecule the locations of helices
              predicted by a number of methods agree moderately well with the
              observed structure, however within the carboxyl half of the
              molecule the overall agreement is poor. For eleven different
              helix predictions, the coefficients giving the correlation
              between prediction and observation range from 0.14 to 0.42. The
              accuracy of the predictions for both beta-sheet regions and for
              turns are generally lower than for the helices, and in a number
              of instances the agreement between prediction and observation is
              no better than would be expected for a random selection of
              residues. The structural predictions for T4 phage lysozyme are
              much less successful than was the case for adenylate kinase
              (Schulz et al. (1974) Nature 250, 140-142). No one method of
              prediction is clearly superior to all others, and although
              empirical predictions based on larger numbers of known protein
              structure tend to be more accurate than those based on a limited
              sample, the improvement in accuracy is not dramatic, suggesting
              that the accuracy of current empirical predictive methods will
              not be substantially increased simply by the inclusion of more
              data from additional protein structure determinations.",
  journal  = "Biochim. Biophys. Acta",
  volume   =  405,
  number   =  2,
  pages    = "442--451",
  month    =  oct,
  year     =  1975,
  language = "en",
  issn     = "0006-3002",
  pmid     = "1180967",
  doi      = "10.1016/0005-2795(75)90109-9"
}

@ARTICLE{Fawcett2006-bq,
  title    = "An introduction to {ROC} analysis",
  author   = "Fawcett, Tom",
  abstract = "Receiver operating characteristics (ROC) graphs are useful for
              organizing classifiers and visualizing their performance. ROC
              graphs are commonly used in medical decision making, and in
              recent years have been used increasingly in machine learning and
              data mining research. Although ROC graphs are apparently simple,
              there are some common misconceptions and pitfalls when using them
              in practice. The purpose of this article is to serve as an
              introduction to ROC graphs and as a guide for using them in
              research.",
  journal  = "Pattern Recognit. Lett.",
  volume   =  27,
  number   =  8,
  pages    = "861--874",
  month    =  jun,
  year     =  2006,
  issn     = "0167-8655",
  doi      = "10.1016/j.patrec.2005.10.010"
}

@ARTICLE{Chen2014-jd,
  title    = "High-throughput platform for real-time monitoring of biological
              processes by multicolor single-molecule fluorescence",
  author   = "Chen, Jin and Dalal, Ravindra V and Petrov, Alexey N and Tsai,
              Albert and O'Leary, Se{\'a}n E and Chapin, Karen and Cheng,
              Janice and Ewan, Mark and Hsiung, Pei-Lin and Lundquist, Paul and
              Turner, Stephen W and Hsu, David R and Puglisi, Joseph D",
  abstract = "Zero-mode waveguides provide a powerful technology for studying
              single-molecule real-time dynamics of biological systems at
              physiological ligand concentrations. We customized a commercial
              zero-mode waveguide-based DNA sequencer for use as a versatile
              instrument for single-molecule fluorescence detection and showed
              that the system provides long fluorophore lifetimes with good
              signal to noise and low spectral cross-talk. We then used a
              ribosomal translation assay to show real-time fluidic delivery
              during data acquisition, showing it is possible to follow the
              conformation and composition of thousands of single biomolecules
              simultaneously through four spectral channels. This instrument
              allows high-throughput multiplexed dynamics of single-molecule
              biological processes over long timescales. The instrumentation
              presented here has broad applications to single-molecule studies
              of biological systems and is easily accessible to the biophysical
              community.",
  journal  = "Proc. Natl. Acad. Sci. U. S. A.",
  volume   =  111,
  number   =  2,
  pages    = "664--669",
  month    =  jan,
  year     =  2014,
  language = "en",
  issn     = "0027-8424, 1091-6490",
  pmid     = "24379388",
  doi      = "10.1073/pnas.1315735111",
  pmc      = "PMC3896158"
}

@ARTICLE{Obermeyer2019-pp,
  title         = "Functional Tensors for Probabilistic Programming",
  author        = "Obermeyer, Fritz and Bingham, Eli and Jankowiak, Martin and
                   Phan, Du and Chen, Jonathan P",
  abstract      = "It is a significant challenge to design probabilistic
                   programming systems that can accommodate a wide variety of
                   inference strategies within a unified framework. Noting that
                   the versatility of modern automatic differentiation
                   frameworks is based in large part on the unifying concept of
                   tensors, we describe a software abstraction for integration
                   --functional tensors-- that captures many of the benefits of
                   tensors, while also being able to describe continuous
                   probability distributions. Moreover, functional tensors are
                   a natural candidate for generalized variable elimination and
                   parallel-scan filtering algorithms that enable parallel
                   exact inference for a large family of tractable modeling
                   motifs. We demonstrate the versatility of functional tensors
                   by integrating them into the modeling frontend and inference
                   backend of the Pyro programming language. In experiments we
                   show that the resulting framework enables a large variety of
                   inference strategies, including those that mix exact and
                   approximate inference.",
  month         =  oct,
  year          =  2019,
  url           = "http://arxiv.org/abs/1910.10775",
  journal       = "arXiv",
  eprint        = "1910.10775",
  primaryClass  = "stat.ML",
  arxivid       = "1910.10775"
}

@ARTICLE{Kschischang2001-lj,
  title    = "Factor graphs and the sum-product algorithm",
  author   = "Kschischang, F R and Frey, B J and Loeliger, H-A",
  abstract = "Algorithms that must deal with complicated global functions of
              many variables often exploit the manner in which the given
              functions factor as a product of ``local'' functions, each of
              which depends on a subset of the variables. Such a factorization
              can be visualized with a bipartite graph that we call a factor
              graph, In this tutorial paper, we present a generic
              message-passing algorithm, the sum-product algorithm, that
              operates in a factor graph. Following a single, simple
              computational rule, the sum-product algorithm computes-either
              exactly or approximately-various marginal functions derived from
              the global function. A wide variety of algorithms developed in
              artificial intelligence, signal processing, and digital
              communications can be derived as specific instances of the
              sum-product algorithm, including the forward/backward algorithm,
              the Viterbi algorithm, the iterative ``turbo'' decoding
              algorithm, Pearl's (1988) belief propagation algorithm for
              Bayesian networks, the Kalman filter, and certain fast Fourier
              transform (FFT) algorithms.",
  journal  = "IEEE Trans. Inf. Theory",
  volume   =  47,
  number   =  2,
  pages    = "498--519",
  month    =  feb,
  year     =  2001,
  issn     = "0018-9448",
  doi      = "10.1109/18.910572"
}

@ARTICLE{Foerster2018-kd,
  title         = "{DiCE}: The Infinitely Differentiable {Monte-Carlo}
                   Estimator",
  author        = "Foerster, Jakob and Farquhar, Gregory and Al-Shedivat,
                   Maruan and Rockt{\"a}schel, Tim and Xing, Eric P and
                   Whiteson, Shimon",
  abstract      = "The score function estimator is widely used for estimating
                   gradients of stochastic objectives in stochastic computation
                   graphs (SCG), eg, in reinforcement learning and
                   meta-learning. While deriving the first-order gradient
                   estimators by differentiating a surrogate loss (SL)
                   objective is computationally and conceptually simple, using
                   the same approach for higher-order derivatives is more
                   challenging. Firstly, analytically deriving and implementing
                   such estimators is laborious and not compliant with
                   automatic differentiation. Secondly, repeatedly applying SL
                   to construct new objectives for each order derivative
                   involves increasingly cumbersome graph manipulations.
                   Lastly, to match the first-order gradient under
                   differentiation, SL treats part of the cost as a fixed
                   sample, which we show leads to missing and wrong terms for
                   estimators of higher-order derivatives. To address all these
                   shortcomings in a unified way, we introduce DiCE, which
                   provides a single objective that can be differentiated
                   repeatedly, generating correct estimators of derivatives of
                   any order in SCGs. Unlike SL, DiCE relies on automatic
                   differentiation for performing the requisite graph
                   manipulations. We verify the correctness of DiCE both
                   through a proof and numerical evaluation of the DiCE
                   derivative estimates. We also use DiCE to propose and
                   evaluate a novel approach for multi-agent learning. Our code
                   is available at https://www.github.com/alshedivat/lola.",
  month         =  feb,
  year          =  2018,
  url           = "http://arxiv.org/abs/1802.05098",
  journal       = "arXiv",
  eprint        = "1802.05098",
  primaryClass  = "cs.LG",
  arxivid       = "1802.05098"
}

@ARTICLE{Obermeyer2019-xt,
  title         = "Tensor Variable Elimination for Plated Factor Graphs",
  author        = "Obermeyer, Fritz and Bingham, Eli and Jankowiak, Martin and
                   Chiu, Justin and Pradhan, Neeraj and Rush, Alexander and
                   Goodman, Noah",
  abstract      = "A wide class of machine learning algorithms can be reduced
                   to variable elimination on factor graphs. While factor
                   graphs provide a unifying notation for these algorithms,
                   they do not provide a compact way to express repeated
                   structure when compared to plate diagrams for directed
                   graphical models. To exploit efficient tensor algebra in
                   graphs with plates of variables, we generalize undirected
                   factor graphs to plated factor graphs and variable
                   elimination to a tensor variable elimination algorithm that
                   operates directly on plated factor graphs. Moreover, we
                   generalize complexity bounds based on treewidth and
                   characterize the class of plated factor graphs for which
                   inference is tractable. As an application, we integrate
                   tensor variable elimination into the Pyro probabilistic
                   programming language to enable exact inference in discrete
                   latent variable models with repeated structure. We validate
                   our methods with experiments on both directed and undirected
                   graphical models, including applications to polyphonic music
                   modeling, animal movement modeling, and latent sentiment
                   analysis.",
  month         =  feb,
  year          =  2019,
  url           = "http://arxiv.org/abs/1902.03210",
  journal       = "arXiv",
  eprint        = "1902.03210",
  primaryClass  = "stat.ML",
  arxivid       = "1902.03210"
}

@ARTICLE{Bingham2019-qy,
  title    = "Pyro: Deep Universal Probabilistic Programming",
  author   = "Bingham, Eli and Chen, Jonathan P and Jankowiak, Martin and
              Obermeyer, Fritz and Pradhan, Neeraj and Karaletsos, Theofanis
              and Singh, Rohit and Szerlip, Paul and Horsfall, Paul and
              Goodman, Noah D",
  journal  = "J. Mach. Learn. Res.",
  volume   =  20,
  number   =  28,
  pages    = "1--6",
  year     =  2019,
  url      = "http://jmlr.org/papers/v20/18-403.html",
  issn     = "1532-4435"
}

@ARTICLE{Crocker1996-vw,
  title    = "Methods of Digital Video Microscopy for Colloidal Studies",
  author   = "Crocker, John C and Grier, David G",
  abstract = "We describe a set of image processing algorithms for extracting
              quantitative data from digitized video microscope images of
              colloidal suspensions. In a typical application, these direct
              imaging techniques can locate submicrometer spheres to within 10
              nm in the focal plane and 150 nm in depth. Combining information
              from a sequence of video images into single-particle trajectories
              makes possible measurements of quantities of fundamental and
              practical interest such as diffusion coefficients and pair-wise
              interaction potentials. The measurements we describe in detail
              combine the outstanding resolution of digital imaging with
              video-synchronized optical trapping to obtain highly accurate and
              reproducible results very rapidly.",
  journal  = "J. Colloid Interface Sci.",
  volume   =  179,
  number   =  1,
  pages    = "298--310",
  month    =  apr,
  year     =  1996,
  issn     = "0021-9797",
  doi      = "10.1006/jcis.1996.0217"
}

@ARTICLE{Grigorieff2016-tt,
  title    = "Frealign: An Exploratory Tool for {Single-Particle} {Cryo-EM}",
  author   = "Grigorieff, N",
  abstract = "Frealign is a software tool designed to process electron
              microscope images of single molecules and complexes to obtain
              reconstructions at the highest possible resolution. It provides a
              number of refinement parameters and options that allow users to
              tune their refinement to achieve specific goals, such as masking
              to classify selected regions within a particle, control over the
              refinement of specific alignment parameters to accommodate
              various data collection schemes, refinement of pseudosymmetric
              particles, and generation of initial maps. This chapter provides
              a general overview of Frealign functions and a more detailed
              guide to using Frealign in typical scenarios.",
  journal  = "Methods Enzymol.",
  volume   =  579,
  pages    = "191--226",
  month    =  jun,
  year     =  2016,
  language = "en",
  issn     = "0076-6879, 1557-7988",
  pmid     = "27572728",
  doi      = "10.1016/bs.mie.2016.04.013",
  pmc      = "PMC6760665"
}

@ARTICLE{Ticau2015-ib,
  title    = "Single-molecule studies of origin licensing reveal mechanisms
              ensuring bidirectional helicase loading",
  author   = "Ticau, Simina and Friedman, Larry J and Ivica, Nikola A and
              Gelles, Jeff and Bell, Stephen P",
  abstract = "Loading of the ring-shaped Mcm2-7 replicative helicase around DNA
              licenses eukaryotic origins of replication. During loading, Cdc6,
              Cdt1, and the origin-recognition complex (ORC) assemble two
              heterohexameric Mcm2-7 complexes into a head-to-head double
              hexamer that facilitates bidirectional replication initiation.
              Using multi-wavelength single-molecule fluorescence to monitor
              the events of helicase loading, we demonstrate that
              double-hexamer formation is the result of sequential loading of
              individual Mcm2-7 complexes. Loading of each Mcm2-7 molecule
              involves the ordered association and dissociation of distinct
              Cdc6 and Cdt1 proteins. In contrast, one ORC molecule directs
              loading of both helicases in each double hexamer. Based on
              single-molecule FRET, arrival of the second Mcm2-7 results in
              rapid double-hexamer formation that anticipates Cdc6 and Cdt1
              release, suggesting that Mcm-Mcm interactions recruit the second
              helicase. Our findings reveal the complex protein dynamics that
              coordinate helicase loading and indicate that distinct mechanisms
              load the oppositely oriented helicases that are central to
              bidirectional replication initiation.",
  journal  = "Cell",
  volume   =  161,
  number   =  3,
  pages    = "513--525",
  month    =  apr,
  year     =  2015,
  language = "en",
  issn     = "0092-8674, 1097-4172",
  pmid     = "25892223",
  doi      = "10.1016/j.cell.2015.03.012",
  pmc      = "PMC4445235"
}

@ARTICLE{Lyumkis2013-fg,
  title     = "Likelihood-based classification of {cryo-EM} images using
               {FREALIGN}",
  author    = "Lyumkis, Dmitry and Brilot, Axel F and Theobald, Douglas L and
               Grigorieff, Nikolaus",
  abstract  = "We describe an implementation of maximum likelihood
               classification for single particle electron cryo-microscopy that
               is based on the FREALIGN software. Particle alignment parameters
               are determined by maximizing a joint likelihood that can include
               hierarchical priors, while classification is performed by
               expectation maximization of a marginal likelihood. We test the
               FREALIGN implementation using a simulated dataset containing
               computer-generated projection images of three different 70S
               ribosome structures, as well as a publicly available dataset of
               70S ribosomes. The results show that the mixed strategy of the
               new FREALIGN algorithm yields performance on par with other
               maximum likelihood implementations, while remaining
               computationally efficient.",
  journal   = "J. Struct. Biol.",
  publisher = "Elsevier",
  volume    =  183,
  number    =  3,
  pages     = "377--388",
  month     =  sep,
  year      =  2013,
  language  = "en",
  issn      = "1047-8477, 1095-8657",
  pmid      = "23872434",
  doi       = "10.1016/j.jsb.2013.07.005",
  pmc       = "PMC3824613"
}

@ARTICLE{Friedman2015-nx,
  title    = "Multi-wavelength single-molecule fluorescence analysis of
              transcription mechanisms",
  author   = "Friedman, Larry J and Gelles, Jeff",
  abstract = "Multi-wavelength single molecule fluorescence microscopy is a
              valuable tool for clarifying transcription mechanisms, which
              involve multiple components and intermediates. Here we describe
              methods for the analysis and interpretation of such single
              molecule data. The methods described include those for image
              alignment, drift correction, spot discrimination, as well as
              robust methods for analyzing single-molecule binding and
              dissociation kinetics that account for non-specific binding and
              photobleaching. Finally, we give an example of the use of the
              resulting data to extract the kinetic mechanism of promoter
              binding by a bacterial RNA polymerase holoenzyme.",
  journal  = "Methods",
  volume   =  86,
  pages    = "27--36",
  month    =  sep,
  year     =  2015,
  language = "en",
  issn     = "1046-2023, 1095-9130",
  pmid     = "26032816",
  doi      = "10.1016/j.ymeth.2015.05.026",
  pmc      = "PMC4577447"
}

@ARTICLE{Harden2016-ho,
  title    = "Bacterial {RNA} polymerase can retain $\sigma$70 throughout
              transcription",
  author   = "Harden, Timothy T and Wells, Christopher D and Friedman, Larry J
              and Landick, Robert and Hochschild, Ann and Kondev, Jane and
              Gelles, Jeff",
  abstract = "Production of a messenger RNA proceeds through sequential stages
              of transcription initiation and transcript elongation and
              termination. During each of these stages, RNA polymerase (RNAP)
              function is regulated by RNAP-associated protein factors. In
              bacteria, RNAP-associated $\sigma$ factors are strictly required
              for promoter recognition and have historically been regarded as
              dedicated initiation factors. However, the primary $\sigma$
              factor in Escherichia coli, $\sigma$(70), can remain associated
              with RNAP during the transition from initiation to elongation,
              influencing events that occur after initiation. Quantitative
              studies on the extent of $\sigma$(70) retention have been limited
              to complexes halted during early elongation. Here, we used
              multiwavelength single-molecule fluorescence-colocalization
              microscopy to observe the $\sigma$(70)-RNAP complex during
              initiation from the $\lambda$ PR' promoter and throughout the
              elongation of a long (>2,000-nt) transcript. Our results provide
              direct measurements of the fraction of actively transcribing
              complexes with bound $\sigma$(70) and the kinetics of
              $\sigma$(70) release from actively transcribing complexes.
              $\sigma$(70) release from mature elongation complexes was slow
              (0.0038 s(-1)); a substantial subpopulation of elongation
              complexes retained $\sigma$(70) throughout transcript elongation,
              and this fraction depended on the sequence of the initially
              transcribed region. We also show that elongation complexes
              containing $\sigma$(70) manifest enhanced recognition of a
              promoter-like pause element positioned hundreds of nucleotides
              downstream of the promoter. Together, the results provide a
              quantitative framework for understanding the postinitiation roles
              of $\sigma$(70) during transcription.",
  journal  = "Proc. Natl. Acad. Sci. U. S. A.",
  volume   =  113,
  number   =  3,
  pages    = "602--607",
  month    =  jan,
  year     =  2016,
  language = "en",
  issn     = "0027-8424, 1091-6490",
  pmid     = "26733675",
  doi      = "10.1073/pnas.1513899113",
  pmc      = "PMC4725480"
}

@BOOK{Bishop2006-oa,
  title     = "Pattern recognition and machine learning",
  author    = "Bishop, Christopher M",
  publisher = "Springer",
  year      =  2006,
  address   = "New York"
}