Showing posts with label systems-biology. Show all posts
Showing posts with label systems-biology. Show all posts

April 3, 2020

NeuroConferences in Twos


Welcome to April and the era of the virtual conference! Aside from enforcing social distancing, virtual conferences have a number of other social benefits. I have recently presented at two virtual conferences, one on Twitter and one via teleconference software. The Twitter conference (OHBMx) was held previously as the brain.tc conference. This year, I presented on behalf of four co-authors about our new paper "Braitenberg Vehicles as Developmental Neurosimulation".


Our talk (#44) at OHBMx (click to enlarge).

In this talk and paper, we explore using Braitenberg Vehicles (BVs) to study the role of processes related to brain development and ontogenetic emergence of behavior. So-called dBVs are flexible systems that allow for naturalistic explorations of embodied behavior. Our approach utilizes four allied topical areas: evolutionary simulations, multisensory Hebbian learning, simulations of collective behavior, and explorations of embodied cognition.

A little more than a week later, me and one of my co-authors from the Twitter conference (Jesse Parent) presented at the Neuromatch conference. Neuromatch was put together in a only a few weeks by Konrad Kording, Dan Goodman, and Titipat Achakulvisut (congrats to them). The organizers used Crowdcast and Zoom as the presentation media. Two days of talks and over 2500 attendees! While there were various technical challenges to overcome (such as Zoombombing), the conference was a great success. The organizers said that this conference was meant as a template for future all-virtual conferences.


The title of my presentation was "Process as Connectivity: towards biology-specific complex networks". This is an update on presentations given at the Find Your Inner Modeler II workshop and the NetSci 2017 conference. Jesse's presentation was "Embodied Cognition: Using Developmental Braitenberg Vehicles To Model Levels of Representation", and while delayed due to technical difficulties, was a follow-up on our dBVs paper.

Two great talks at Neuromatch! Click to enlarge.

The other part of Neuromatch is matching researchers based on interest area. One interesting outcome to result from this matching process is the new BrainWeb community. BrainWeb is a new collaborative platform aimed at bringing together Neuroscientists and Neuro-adjacent people with expertise to share. They have even visualized an adjacency matrix of the community so far based on expertise. Check out their website for information on hackathon times and virtual locations (URLs).


Now it is I who is caught up in the hairball! Click to enlarge.

UPDATE (4/6): a new paper from several eLife Ambassadors is now out on the bioRxiv with recommendations on how to improve the academic conference experience. Many of their concerns and recommendations for change dovetail with the virtual conference experience. 

Citation: Sarabipour et.al (2020). Evaluating features of scientific conferences: A call for improvements. biorxiv, doi:10.1101/2020.04.02.022079.

January 1, 2019

January is DevoWorm month!

Blossoms or fireworks to ring in the New Year?


Welcome to 2019! And welcome to OpenWorm Foundation's project of the month for January, featuring DevoWorm. Here I will briefly go over progress in the DevoWorm group over the last year and a half. If you would like to know more, we have a group Slack channel (#devoworm) in the OpenWorm team, a group website, and a Github repository.


For the uninitiated, the DevoWorm group has a multifaceted set of interests. We are interested in simulating and analyzing data related to worm development, but have an interest in the development of other model organisms as well. In terms of results, we have focused mostly on publications and open datasets, but as you will see from the website, we have also been involved in the creation of unique demos and software development.

The DevoWorm group is also interested in education. Our educational efforts have largely spread out over four types of pedagogy: digital badges, tutorials via interactive notebooks, public lectures, and one-on-one mentorship through the Google Summer of Code (GSoC) program. The OpenWorm Foundation has hosted a DevoWorm GSoC student for the past two years (2017 and 2018), and will be offering a third opportunity this year (2019). 

This is the 15th anniversary for the GSoC program, and it is always an excellent experience. The application process begins on February 25th. If you are interested in a mixture of computational biology, image processing, and machine learning, please contact us for more information.

COURTESY: Image from "One, Two, Three,....GSoC!" by Vipal Gupta

While GSoC is well-compensated opportunity to participate in DevoWorm, there are also less formal ways through which one can collaborate. One of these ways is through a conventional research pathway such as analyzing data, building a simulation, or curating a dataset. Another way to collaborate is to help create new types of educational content. We are particularly interested in creating virtual reality-based offerings in the near future. If you enjoy creating educational content, or simply enjoy learning, please get in touch!

Another new initiative is called DevoZoo. The DevoZoo site aggregates open datasets, methods, and techniques relevant to computational developmental biology and data science biology. We currently host open datasets for the following model organisms: C. elegans, Drosophila, Zebrafish, Ascidians, and Mouse. DevoZoo also hosts raw microscopy data in the form of movies for many of these model organisms as well as Spiders. As if this were not enough, we also try to engage learners and open scientists with artificial life models. The DevoZoo presents three: Morphozoans, developmental Braitenberg Vehicles, and Multicell Systems. The artificial life models in particular could use some further development. Check out the DevoZoo webpage or ask us if you would like to learn more.



Finally, you can participate by collaborating on a publication. The DevoWorm group has been featured in four publications in the past year. The OpenWorm article in the "Connectome to Behavior" special issue of Royal Society B provides a succinct description of the project and its current course. Some of our members served as editors and contributors to a special issue of BioSystems in honor of Dr. Lev Beloussov. This issue features 32 articles that provide a very broad and innovative look at the topic of morphogenesis. Our set of contributions (peer-reviewed papers) spanned from network models of the embryo to the developmental emergence of the connectome and quantitative approaches to organogenesis in the eye imaginal disc.

If you are interested in joining in on the discussion, we hold group meetings online every Monday at 9pm UTC. We are also starting to host hackathons on Fridays during the late morning/early afternoon North American time. Check out our scheduling page for more information. Hope to encounter you soon, and have a great month!

September 30, 2018

Finding Your Inner Modeler (Part II)

Last year, I attended a workshop at the University of Illinois-Chicago called "Finding Your Inner Modeler". Sponsored by the NSF, FYIM is meant to bring together biologists and modelers and to foster collaborations between the two. There were many interesting talks over the course of two days, including plant biology, biochemical kinetics, and (of course) various types of computational and statistical model [1].

This year was the second installment of FYIM, and this time I was chosen for a platform presentation. The platform presentation (Process as Connectivity: models of interaction in cellular systems) involves a 40-minute discussion between the principal investigator and an expert modeler. For my talk, this expert modeler was Dr. Eric Deeds from the University of Kansas.



The talk features work with several collaborators, features work from the DevoWorm group. In the talk, I described the DevoWorm group as an example of data science biology [2]. As an affiliate of the OpenWorm Foundation [3], the DevoWorm group works with primary and secondary data, and produces secondary and tertiary open datasets that serve as material for publications, student projects, and the wider development/computational biology communities.



The core innovation introduced in this talk is the use of graph theory and complex networks to analyze the organizational structure of the embryonic phenotype. This work is now showcased in a new paper [4] and Github repository.




NOTES:
[1] One example is the Virtual Cell software project, which allows one to model and analyze representations of kinematics, kinetics, geometry, and network interactions at the cellular level.

[2] Alicea, B., Gordon, R., and Portegys, T.E. (2018). DevoWorm: data-theoretical synthesis of C. elegans development. bioRxiv, doi:10.1101/282004.
 
[3] Sarma, G.P., Lee, C-W., Portegys, T., Ghayoomie, V., Jacobs, T., Alicea, B., Cantarelli, M., Currie, M., Gerkin, R.C., Gingell, S., Gleeson, P., Gordon, R., Hasani, R.M., Idili, G., Khayrulin, S., Lung, D., Palyanov, A., Watts, M., Larson, S.D. (2018). OpenWorm: overview and recent advances in integrative biological simulation of Caenorhabditis elegans. Philosophical Transactions of the Royal Society B, 373, 20170382. doi:10.1098/rstb.2017.0382.

[4] Alicea, B. and Gordon R. (2018). Cell Differentiation Processes as Spatial Networks: identifying four-dimensional structure in embryogenesis. BioSystems, doi:10.1016/j.biosystems.2018.09.009.



September 10, 2018

OpenWorm: Royal Society B special issue now live!

Worm images courtesy of the OpenWorm browser (Drs. Christian Grove and Padraig Gleeson)

Regular readers of this blog might recall that the OpenWorm Foundation spearheaded a workshop (From Connectome to Behavior) at the Royal Society (London) in January 2018. This workshop generated a lot of social media content and internal (to OpenWorm Slack) discussion of the presented topics.

Since then, the participants have been hard at work putting together a special issue (now live in Royal Society B) that presents in more detail what was discussed at the meeting. Lots of great papers on interesting topics ranging from network theory to movement models, and from foraging behavior to quantitative phenotyping.

Many of these papers feature ongoing work related to the OpenWorm Foundation, including the Geppetto, c302, and Sibernetic projects. There is also an OpenWorm overview paper that provides a current state of the initiative. Enjoy!

August 1, 2018

OpenWorm Blog: August is ChannelWorm Month!

Content is being cross-posted from OpenWorm Foundation blog

August is ChannelWorm Month at OpenWorm!

As we make steady progress on our goal of building the world’s first detailed simulation of C. elegans, we’ve been brainstorming ways to systematically draw attention to each of the components of OpenWorm's platform.

Our scientific and outreach committees have decided that each month will be dedicated to a specific repository that will be designated “Project of the Month.”

This coming month (August 2018) will be dedicated to ChannelWorm, a repository aimed at constructing quantitative models of ion channel behavior.

Visit our Github repo and take a look for yourself: https://github.com/openworm/ChannelWorm
See also the Heroku App for extensive curated data on ion channels: https://chopen.herokuapp.com

WHAT ARE ION CHANNELS? Ion channels are pore-forming proteins which facilitate the movement of charged particles (ions) between the extracellular space and the cytoplasm.  All cells contain ion channels and play a central role in normal cellular function.  However, their role in the nervous system is much more significant.  In particular, ion channels in the nervous system mediate the generation of action potentials, the fundamental mechanism by which a network of neurons processes information. 


HOW THIS CONTRIBUTES TO THE OPENWORM VISION: Ion channels are the most granular level of detail in OpenWorm.  In other words, we abstract away the many complexities of intra-cellular function and treat the organism as an information processing system which uses electrical signals to mediate body movement.  Incorporating additional levels of biological detail is certainly a possibility but is not currently on our scientific roadmap.
BRIEF OVERVIEW OF CHANNELWORM: The aim of ChannelWorm is to build quantitative models of ion channel function.  To that end, we use the following workflow:
  • Create a database of information about C. elegans ion channels specifying channel type and location in the nervous system (i.e. name of neuron) where the channel is expressed. 
  • Identify relevant scientific papers which contain experimental recordings of ion channel behavior.
  • Extract plots from the corresponding papers and add them to the database of ion channels. (This data is currently available at https://chopen.herokuapp.com)
  • Digitize plots to extract data points.
  • Use parameter fitting techniques to determine numerical values of parameters for quantitative models.
  • Export ion channel models in the NeuroML (NML) format to be stored in PyOpenWorm.
SHARE IN THE COMMUNITY! We very much encourage both new and experienced volunteers to turn their attention to ChannelWorm and find areas that might be of interest to them.  The best way to get involved is to first fill out our volunteer application form.

In the meantime, we recommend taking a look at the Github repository for ChannelWorm for open issues the project is currently tackling.  Some of the issues are specifically marked as being appropriate for beginners.  We will add to this list over the next few weeks.

WHAT HAPPENS AFTER THE APPLICATION: After we look at your application, you’ll receive an invitation to join our workspace on Slack.  From there, you can contact other volunteers who can help find a project to match your skills and interests.

WHAT IF I’M NOT A PROGRAMMER? Even if you are not a computer programmer, you can still contribute! Here are some of the ways:
  • Author a blog post: we’d love to have informative scientific blog posts on anything relevant to ion channel function and modeling. Submit a draft and we will host it on the OpenWorm blog.
  • Literature search and data re-evaluation: we’d also like to support basic science in this area. If you have experience with conducting research, please get in touch!
  • Create educational content: we can support educational initiatives such as the creation of digital badges and video tutorials. Pitch an idea and become part of the conversation!
  • Something original: if you have an idea for something that no one has thought of, we’d love to hear your proposal!  Artwork, animations, popular scientific articles, etc. are all welcome.  
At the end of August, we’ll be organizing a distributed hackathon for the community to get together and work on tackling open items on our to-do list. We’ll announce more details towards the second week of August.


OW Science Committee is held at 3:00pm UTC, link provided in Slack #science channel. Hackathon Time/Date: TBA. Digital badges are located at badgelist.com/openworm.

We hope you can join us!
Please fill out our volunteer application form and contact us on Slack for more information!

ChannelWorm is currently building upon the work featured in this publication:

Gurkiewicz, M. and Korngreen, A. (2007). A Numerical Approach to Ion Channel Modelling Using Whole-Cell Voltage-Clamp Recordings and a Genetic Algorithm. PLoS Computation Biology, 3(8), e169. https://doi.org/10.1371/journal.pcbi.0030169

February 1, 2018

Things that Just Happened in London.....


This week, the Royal Society is hosting a workshop called "From Connectome to Behavior", hosted by the OpenWorm Foundation. A program can be found here


The Monday and Tuesday sessions included talks by OpenWorm senior contributors as well as mathematical, biological, and engineering researchers from around the world (including John White, a C. elegans  research legend). Fortunately, you can get a taste for the topical diversity on the OpenWorm Twitter feed, and from the screenshots below.









The Wednesday session was a day for demos and less formal talks, as evidenced by the robotics contingent showing off their latest hardware. Living worms also made an appearance!





How good is the OpenWorm simulation suite? Take a simple test: which one is the real worm, the worm on the left or the worm on the right? View the video footage and vote here.



Here is some OpenWorm-related artwork on display, designs by Matteo Farinella


If what you see here looks good and you would like to learn more, please get in touch with the OpenWorm community! Hope to see you soon!


Thanks to the Royal Society of London for being an excellent host!


November 15, 2017

Deep Reading Brings New Things to Life (Science)

Here is an interesting Twitter thread from Jacquelyn Gill on 'deep reading':


The basic idea is that exploring older literature can lead to new insights, which in turn lead to new research directions. The new research of our era tends to focus on the most relevant and cutting-edge literature [1]. This recency bias excludes many similarly relevant articles, including articles that perhaps inspired the more recent citations to begin with [2]. 

I have my own list of deep reads that have influenced some of my research in a similar fashion. These references can be either foundational or so-called "sleeping beauties" [3]. Regardless, I am doing my part to maintain connectivity [4] amongst academic citation networks:


1) Woodger, J.H. The Axiomatic Method in Biology. 1937.

An argument for biological rules, an influence on cladistics (developed in the 1960s), and a natural bridge to geometric approaches to data analysis and modeling. While there is a strong argument to be made against the axiomatic approach [5], this directly inspired much of my thinking in the biological modeling area. 


2) Davis R.L., Weintraub H., and Lassar A.B. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell 51, 987–1000. 1987.

This was the first proof-of-concept for direct cellular reprogramming, and predates the late 2000's Nobel-winning work in stem cells by decades. In this case, a single transcription factor (MyoD) was used to convert a cell from one phenotype to another without a strict regard for function. More generally, this paper helped inspired my thinking in the area of cellular reprogramming to go beyond a biological optimization or algorithmic approach [6].


3) Ashby, W.R. Design for a Brain. 1960.

"Design for a Brain" serves as a stand-in for the entirely of Ashby's bibliography, but this is the best example of how Ashby successfully merged explanations of adaptive behavior [7] with systems models (cybernetics). In fact, Ashby originally coined the phrase "Intelligence Augmentation" [8]. I first discovered Ashby's work while working in the area of Augmented Cognition, and has been more generally useful as inspiration for complex systems thinking.



Not so much a couple of sleeping beauty as easy reading technical reference guides for all things complexity theory.


5) Bourdieu, P. Outline of a Theory of Practice. Cambridge University Press. 1977 AND Alexander, C., Ishikawa, S., and Silverstein, M. A Pattern Language: towns, buildings, construction. Oxford
University Press. 1977.

This is a bonus, not because the references are particularly obscure or even from the same academic field, but because they partially influenced my own view of cultural evolution. This is yet another piece of advice to young researchers: take things that appear to be disparate on their surface and incorporate them into your mental model. If nothing else, you will gain valuable skills in intellectual synthesis.

UPDATE (11/17):
Here is another example of old (classic, not outdated) work influencing new scholarship.



NOTES:
[1] Evans, J.A. (2008). Electronic Publication and the Narrowing of Science and Scholarship. Science, 321(5887), 395-399 AND Scheffer, M. (2014). The forgotten half of scientific thinking. PNAS, 111(17), 6119.

[2] related topics discussed on this blog include distributions of citation ages and most-cited papers.

[3] van Raan, A.F.J. (2004). Sleeping Beauties in Science. Scientometrics, 59(3), 467–472.

[4] Editors (2010). On citing well. Nature Chemical Biology, 6, 79.

[5] For the semantic approach (which had been influential to my more recent work), please see: Lloyd, E.A. (1994). The Structure and Confirmation of Evolutionary Theory. Princeton University Press, Princeton, NJ.

[6] Ronquist, S. et.al (2017). Algorithm for cellular reprogramming. PNAS, 114(45), 11832–11837.

[7] Sterling, P. and Eyer, J. (1988). Allostasis: A new paradigm to explain arousal pathology. In "Handbook of life stress, cognition, and health". Fisher, S. and Reason, J.T. eds. Wiley, New York. 

[8] Ashby, W.R. (1956). An Introduction to Cybernetics. Springer, Berlin.

February 9, 2017

OpenWorm Open House Videos

To recap from a previous post, the OpenWorm Foundation held its first virtual Open House in October in order to showcase all current projects and their status. After a YouTube video streaming snafu and a period of playing video capture catch-up, the YouTube portion of the OpenWorm Open House is now live! 


The first Open House YouTube playlist is the Flash talk series,which covers all of the projects under the Foundation's umbrella. This playlist currrently includes all but two videos on the session program. While the original stream is being repaired, please check out the playlists.


The second Open House YouTube playlist features two tutorials (longer sessions of 45 minutes) that originally ran in parallel. We also have an permenant and citable archive at Figshare (doi:10.6084/ m9.figshare.4331036), which includes the videos along with supplemental papers and presentations. While the download is large, it is worth checking out. Enjoy!

September 6, 2016

Now Announcing the OpenWorm Open House

OpenWorm Browser. Courtesy Christian Grove, WormBase and Caltech.

About two years ago, I announced the start of the DevoWorm project to the OpenWorm community. Now both OpenWorm and DevoWorm have grown up a bit, with the former (OpenWorm) now being a Foundation and the latter (DevoWorm) resulting in multiple publications. Now we will be celebrating all of the projects that make up the OpenWorm Foundation in an Open House format, taking place in cyberspace and tentatively scheduled for October.

Image courtesy Matteo Farinella: http://matteofarinella.com/Open-Worm. These posters are the outcome of an OpenWorm Kickstarter campaign several years ago.

The details of the schedule are still being worked out, but the format is to include both short, 5-minute talks (Ignite-style) and longer tutorials (45-60 minutes, plus questions). The short talks will highlight the various ongoing projects within OpenWorm, while the tutorials will focus on specific methods or procedures employed by the projects. If you happen to be a project leader or major contributor, I have probably already asked you for content. Interested in either contributing content or attending? Please let me know

Dr. Stephen Larson (pre-PhD), discussing the connection between Lt. Data and C. elegans at Ignite San Diego.

I have also been involved in committee work for the OpenWorm foundation. One of the initiatives we are in the process of establishing is the OpenWorm badge system, which is being spearheaded by Dr. Chee-Wai Lee. Currently trendy in the online learning world, this is an experiment in open learning that provides micro-credentials to a global community. Badges are a great way to learn new skills, as well as a means to motivate people's contributions to different projects within OpenWorm. Currently, OpenWorm is offering tutorials on the Hodgkin-Huxley model, the Muscle Model builder, and the Muscle Model explorer. If there are any tutorials you would like to see us offer, or if you think there is a need for a particular skill to be highlighted, please let me know.

August 19, 2016

From Toy Models to Quantifying Mosaic Development

Time travel in the Terminator metaverse. COURTESY: Michael Talley.

Almost two years ago, Richard Gordon and I published a paper in the journal Biosystems called "Toy Models for Macroevolutionary Patterns and Trends" [1]. Now, almost exactly two years later [2], we have published a second paper (not quite a follow-up) called "Quantifying Mosaic Development: towards an evo-devo postmodern synthesis of the evolution of development via differentiation trees of embryos". While the title is quite long, the approach can be best described as computational/ statistical evolution of development (evo-devo).

Sketch of a generic differentiation tree, which figures prominently in our theoretical synthesis and analysis. COURTESY: Dr. Richard Gordon.

This paper is part of a special issue in the journal Biology called "Beyond the Modern Evolutionary Synthesis- what have we missed?" and a product of the DevoWorm project. The paper itself is a hybrid theoretical synthesis/research report, and introduces a variety of comparative statistical and computational techniques [3] that are used to analyze quantitative spatial and temporal datasets representing early embryogenesis. Part of this approach was previewed in our most recent public lecture to the OpenWorm Foundation.

The comparative data analysis involves investigations within and between two species from different parts of the tree of life: Caenorhabditis elegans (Nematode, invertebrate) and Ciona intestinalis (Tunicate, chordate). The main comparison involves different instances of early mosaic development, or a developmental process that is deterministic with respect to cellular fate. We also reference data from the regulative developing Axolotl (Amphibian, vertebrate) in one of the analyses. All of the analyses involve the reuse and analysis of secondary data, which is becoming an important part of the scientific process for many research groups.

One of the techniques featured in the paper is an information-theoretic technique called information isometry [4]. This method was developed within the DevoWorm group, and uses a mathematical representation called an isometric graph to visualize cell lineages organized in different ways (e.g. a lineage tree vs. a differentiation tree). This method is summarized and validated in our paper "Information Isometry Technique Reveals Organizational Features in Developmental Cell Lineages" [4]. Briefly, each level of the cell lineage is represented as an isoline, which contains points of a specific Hamming distance. The Hamming distance is the distance between that particular cell in two alternative cell lineage orderings (the forementioned lineage and differentiation trees).

An example of an isometric graph from Caenorhabditis elegans, taken from Figure 12 in [5]. The position of a point representing a cell is based on the depth of its node in the cell lineage. The positions of all points are rotated 45 degrees clockwise from a bottom-to-top differentiation tree (in this case) ordering, where the one-cell stage is at the bottom of the graph.

A final word on the new Biology paper as it related to the use of references. Recently, I ran across a paper called "The Memory of Science: Inflation, Myopia, and the Knowledge Network" [6], which introduced me to the statistical definition of citation age. This inspired me to calculate the citation age of all journal references from three papers: Toy Models, Quantifying Mosaic Development, and a Nature Reviews Neuroscience paper from Bohil, Alicea (me), and Biocca, published in 2011. This was used as an analytical control -- as it is a review, it should contain papers which are older than the contemporary literature. Here are the age distributions for all three papers.

Distribution of Citation Ages from "Toy Models for Macroevolutionary Patterns and Trends" (circa 2014).

Distribution of Citation Ages from "Quantifying Mosaic Development: Towards an Evo-Devo Postmodern Synthesis of the Evolution of Development Via Differentiation Trees of Embryos" (circa 2016).


Distribution of Citation Ages from "Virtual Reality in Neuroscience Research and Therapy" (circa 2011).

What is interesting here is that both "Toy Models" and "Quantifying Mosaic Development" show a long tail with respect to age, while the review article shows very little in terms of a distributional tail. While there are differences in topical literatures (the VR and associated perceptual literature is not that old, after all) that influence the result, it seems that the recurrent academic Terminators utilize the literature in a way somewhat differently than most contemporary research papers. While the respect for history is somewhat author and topically dependent, it does seem to add a extra dimension to the research.


NOTES:
[1] the Toy Models paper was part of a Biosystems special issue called "Patterns in Evolution".

[2] This is a Terminator metaverse reference, in which the Terminator comes back every ten years to cause, effect, and/or stop Judgement Day.

[3] Gittleman, J.L. and Luh, H. (1992). On Comparing Comparative Methods. Annual Review of Ecology and Systematics, 23, 383-404.

[4] Alicea, B., Portegys, T.E., and Gordon, R. (2016). Information Isometry Technique Reveals Organizational Features in Developmental Cell Lineages. bioRxiv, doi:10.1101/062539

[5] Alicea, B. and Gordon, R. (2016). Quantifying Mosaic Development: Towards an Evo-Devo Postmodern Synthesis of the Evolution of Development Via Differentiation Trees of Embryos. Biology, 5(3), 33.

[6] Pan, R.K., Petersen, A.M., Pammolli, F., and Fortunato, S. (2016). The Memory of Science: Inflation, Myopia, and the Knowledge Network. arXiv, 1607.05606.

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