Friday, October 4, 2013

Neural circuits that control REM sleep in mice identified

October 4, 2013

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Out like a light: laser light controls REM sleep in mice (credit: Douglas Institute)

Scientists have controlled the duration of REM (rapid eye movements, associated with dreaming) sleep in mice by activating melanin-concentrating hormone (MCH)-expressing neurons in the lateral hypothalamus, using optogenetics (controlling neuronal activity with light).
“These research findings could help us better grasp how the brain controls sleep and better understand the role of sleep in humans. These results could also lead to new therapeutic strategies to treat sleep disorders along with associated neuropsychiatric problems,” said Dr. Antoine Adamantidis, who led the research.
He is an assistant professor at McGill University, a researcher at Douglas Institute, and is the Canada Research Chair in Neural Circuits and Optogenetics.
“This research will eventually lead to the identification of new therapeutic targets for treatment of sleep disorders (insomnia, fragmented sleep, etc.) as well as sleep disturbances associated with psychiatric disorders (such as major depression and schizophrenia),” Adamantidis explained to KurzweilAI.

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Using optogenetic laser light for acute activation of lateral hypothalamus MCH neurons at the onset of REM sleep extended the duration of REM (but not non-REM) sleep episodes (credit: Sonia Jego et al., Nature Neuroscience)

“In a previous studies , we identified hypocretin/orexin (Adamantidis et al., Nature 2007) and norepinephrine (Carter et al., 2009 Nat. Neurosci.) neurons as important arousal circuits.”
Researchers at Howard Hughes Medical Institute, Rockefeller University Laboratory of Molecular Genetics, MRC National Institute for Medical Research, and King’s College London where also involved.
Research funding was provided by Human Frontier Science Program, Canada Foundation for Innovation, Canadian Research Chair Program (Tier 2 Chair), Canadian Institutes of Health Research (CIHR), Natural Sciences and Engineering Research Council of Canada (NSERC), Fonds de Recherche du Québec – Santé (FRQS), McGill University, and Douglas Institute Foundation.

Abstract of Nature Neuroscience reference

Rapid-eye movement (REM) sleep correlates with neuronal activity in the brainstem, basal forebrain and lateral hypothalamus. Lateral hypothalamus melanin-concentrating hormone (MCH)-expressing neurons are active during sleep, but their effects on REM sleep remain unclear. Using optogenetic tools in newly generated Tg(Pmch-cre) mice, we found that acute activation of MCH neurons (ChETA, SSFO) at the onset of REM sleep extended the duration of REM, but not non-REM, sleep episodes. In contrast, their acute silencing (eNpHR3.0, archaerhodopsin) reduced the frequency and amplitude of hippocampal theta rhythm without affecting REM sleep duration. In vitro activation of MCH neuron terminals induced GABAA-mediated inhibitory postsynaptic currents in wake-promoting histaminergic neurons of the tuberomammillary nucleus (TMN), and in vivo activation of MCH neuron terminals in TMN or medial septum also prolonged REM sleep episodes. Collectively, these results suggest that activation of MCH neurons maintains REM sleep, possibly through inhibition of arousal circuits in the mammalian brain.

(¯`*• Global Source and/or more resources at http://goo.gl/zvSV7 │ www.Future-Observatory.blogspot.com and on LinkeIn Group's "Becoming Aware of the Futures" at http://goo.gl/8qKBbK │ @SciCzar │ Point of Contact: www.linkedin.com/in/AndresAgostini

Cells from small biopsies can be used to grow large numbers of a patient’s own protective brain cells

October 4, 2013

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Cells from brain biopsy for patient with Parkinson’s disease.Scale bar: 50 microns. (Credit: Hu Xu et al./The FASEB Journal)

Scientists at the University of Western Ontario in Canada enrolled patients with Parkinson’s disease who were scheduled to have deep brain stimulation (DBS) surgery and removed small biopsies near the surface of the brain.
They then multiplied the cells in culture to generate millions of patient-specific cells that were then subjected to genetic analysis.
These cells exhibited regeneration and characteristics of a fundamental class of brain cells, called glia. The cells expressed a broad array of natural and potent protective agents, called neurotrophic factors.
“It is our hope that the results of this study provide a footing for further advancement of personalized, cell-based treatments for currently incurable and devastating neurological disorders,” said Matthew O. Hebb, M.D., Ph.D., FRCSC, a researcher involved in the work from the Departments of Clinical Neurological Sciences (Neurosurgery), Oncology and Otolaryngology at the University of Western Ontario in Canada.
Such lab-grown therapeutic brain cells could be used in the future to treat a wide range of neurological conditions like Parkinson’s, and also express a broad array of natural and potent protective agents providing preservation and protection against injury, toxins and diseases.

(¯`*• Global Source and/or more resources at http://goo.gl/zvSV7 │ www.Future-Observatory.blogspot.com and on LinkeIn Group's "Becoming Aware of the Futures" at http://goo.gl/8qKBbK │ @SciCzar │ Point of Contact: www.linkedin.com/in/AndresAgostini

MIT inventor unleashes hundreds of self-assembling cube swarmbots

October 4, 2013

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Self-assembling swarming microbots (credit: MIT)

The experts said it couldn’t be done. But research scientist John Romanishin of MIT’s Computer Science and Artificial Intelligence Laboratory (CSAIL) has created M-Blocks — cube robots with no external moving parts.
Despite that, they can magically climb over and around one another, leap through the air, roll across the ground, snap together into different shapes, and even move while suspended upside down from metallic surfaces.
Self-assembling swarmbots
Imagine hordes of swarming microbots that can self-assemble, like the “liquid steel” androids in the movie “Terminator II.”
Armies of these mobile cubes could temporarily repair bridges or buildings during emergencies. These cubes could assemble into different types of furniture or heavy equipment as needed. And they could swarm into environments hostile or inaccessible to humans, diagnose problems, and then reorganize themselves to provide solutions.
They could even be special-purpose cubes: containing cameras, or lights, or battery packs, or other equipment that the mobile cubes could transport.
How M-Blocks work

A prototype of a new modular robot, with its innards exposed and its flywheel — which gives it the ability to move independently — pulled out (credit: M. Scott Brauer, MIT)

The trick: a flywheel that can reach speeds of 20,000 revolutions per minute. When the flywheel is braked, it imparts its angular momentum to the cube. And on each edge of an M-Block and on every face, cleverly arranged permanent magnets allow any two cubes to attach to each other.
To compensate for its static instability, the researchers’ robot relies on some ingenious engineering. On each edge of a cube are two cylindrical magnets, mounted like rolling pins.
When two cubes approach each other, the magnets naturally rotate, so that north poles align with south, and vice versa. Any face of any cube can thus attach to any face of any other.
The cubes’ edges are also beveled, so when two cubes are face to face, there’s a slight gap between their magnets. When one cube begins to flip on top of another, the bevels, and thus the magnets, touch. The connection between the cubes becomes much stronger, anchoring the pivot. On each face of a cube are four more pairs of smaller magnets, arranged symmetrically, which help snap a moving cube into place when it lands on top of another.
A cube army
The MIT researchers are currently building an army of 100 cubes, each of which can move in any direction, and designing algorithms to guide them. “We want hundreds of cubes, scattered randomly across the floor, to be able to identify each other, coalesce, and autonomously transform into a chair, or a ladder, or a desk, on demand,” Romanishin says.
Romanishin, robotics professor Daniela Rus, and postdoc Kyle Gilpin will present a paper describing their new robots at the IEEE/RSJ International Conference on Intelligent Robots and Systems in Japan in November.

Topics: AI/Robotics

(¯`*• Global Source and/or more resources at http://goo.gl/zvSV7 │ www.Future-Observatory.blogspot.com and on LinkeIn Group's "Becoming Aware of the Futures" at http://goo.gl/8qKBbK │ @SciCzar │ Point of Contact: www.linkedin.com/in/AndresAgostini

Thursday, October 3, 2013

’4D printing’ adaptive materials

October 3, 2013

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Example of a programmable 4D material: photo-morphing of initially flat hydrogel sample into various shapes by illumination (credit: Anna C. Balazs)

Researchers from three universities are proposing to add a dimension to 3D printing by developing “4D” materials that can exhibit behavior that changes over time.
Imagine an automobile coating that changes its structure to adapt to a humid environment or a salt-covered road, better protecting the car from corrosion. Or consider a soldier’s uniform that could alter its camouflage or more effectively protect against poison gas or shrapnel upon contact.
With an $855,000 three-year grant from the United States Army Research Office, the researchers from the University of Pittsburgh’s Swanson School of Engineering, Harvard School of Engineering and Applied Sciences, and the University of Illinois plan to manipulate materials at nano and micro levels.
The goal: produce, via 3D printing, materials that can modify their structures over time at the macro level.
Adaptive biomimetic composites
“Rather than construct a static material or one that simply changes its shape, we’re proposing the development of adaptive, biomimetic composites that reprogram their shape, properties, or functionality on demand, based upon external stimuli,” said principal investigator Anna C. Balazs, the Robert v. d. Luft Distinguished Professor of Chemical Engineering in Pitt’s Swanson School of Engineering and a researcher in the computational design of chemo-mechanically responsive gels and composites.
“By integrating our abilities to print precise, three-dimensional, hierarchically-structured materials; synthesize stimuli-responsive components; and predict the temporal behavior of the system, we expect to build the foundation for the new field of 4D printing.”
Co-investigators are Jennifer A. Lewis, the Hansjörg Wyss Professor of Biologically Inspired Engineering at the Harvard School of Engineering and Applied Sciences and an expert in 3D printing of functional materials; and Ralph G. Nuzzo, the G. L. Clark Professor of Chemistry and Professor of Materials Science and Engineering at the University of Illinois, a synthetic chemist who has created novel stimuli-responsive materials.
Lewis added that current 3D printing technology allows the researchers to build in complicated functionality at the nano and micro levels within specific areas of the structure. “Composites that can be reconfigured in the presence of different stimuli could dramatically extend the reach of 3D printing.”
The research will use responsive fillers embedded within a stimuli-responsive hydrogel. Nuzzo says this opens new routes for producing the next generation of smart sensors, coatings, textiles, and structural components.
“The ability to create one fabric that responds to light by changing its color, and to temperature by altering its permeability, and even to an external force by hardening its structure, becomes possible through the creation of responsive materials that are simultaneously adaptive, flexible, lightweight, and strong. It’s this ‘complicated functionality’ that makes true 4D printing a game changer.”

The secret of longevity for the world’s longest-living rodent: better protein creation

October 3, 2013

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Naked mole rats are small, hairless, subterranean rodents native to eastern Africa (credit: Adam Fenster/University of Rochester)

Better-constructed proteins could explain why naked mole rats live long lives — about 30 years — and stay healthy until the very end, resisting cancer, say University of Rochester biologists Vera Gorbunova and Andrei Seluanov.
Their work focuses on naked mole rat ribosomes, which assemble amino acids into proteins. Ribosomes are composed of ribosomal RNA (rRNA) molecules and proteins.
When the ribosome connects amino acids together to create a protein, a mistake is occasionally introduced when an incorrect amino acid is inserted. But the researchers found that the proteins made by naked mole rat cells are up to 40 times less likely to contain such mistakes than the proteins made by mouse cells.
Gorbunova and Seluanov discovered a possible reason: the naked mole rat’s rRNA is unique.
Unique rRNA pattern

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Naked mole rat rRNA in this NMR image shows an unusual pattern with cleaved 28S pattern: 3 bands, instead of 2 with mouse (credit: Jorge Azpurua et al./PNAS)

After applying a dye to a sample, they studied it under ultraviolet light. They found three dark bands — representing concentrations of different rRNA molecules — not the two bands that are characteristic of all other animals, suggesting that there is a “hidden break” in the naked mole rat rRNA.
When its rRNA strands cleave (split) at two specific locations, instead of floating off on their own, two remaining pieces from each strand stay close to each other. They act as a scaffold on which ribosomal proteins are assembled to create a functional ribosome, preventing aberrations. “This is important because proteins with no aberrations help the body to function more efficiently,” said Seluanov.
The next step for the biologists is to split mouse rRNA in the same way to see if it would lead to improved protein creation.
The two biologists hope their work will eventually result in pharmaceutical treatments that modulate protein synthesis in humans, though any medical solution is a long way off, they say.

Abstract for PNAS paper
The naked mole-rat (Heterocephalus glaber) is a subterranean eusocial rodent with a markedly long lifespan and resistance to tumorigenesis. Multiple data implicate modulation of protein translation in longevity. Here we report that 28S ribosomal RNA (rRNA) of the naked mole-rat is processed into two smaller fragments of unequal size. The two breakpoints are located in the 28S rRNA divergent region 6 and excise a fragment of 263 nt. The excised fragment is unique to the naked mole-rat rRNA and does not show homology to other genomic regions. Because this hidden break site could alter ribosome structure, we investigated whether translation rate and amino acid incorporation fidelity were altered. We report that naked mole-rat fibroblasts have significantly increased translational fidelity despite having comparable translation rates with mouse fibroblasts. Although we cannot directly test whether the unique 28S rRNA structure contributes to the increased fidelity of translation, we speculate that it may change the folding or dynamics of the large ribosomal subunit, altering the rate of GTP hydrolysis and/or interaction of the large subunit with tRNA during accommodation, thus affecting the fidelity of protein synthesis. In summary, our results show that naked mole-rat cells produce fewer aberrant proteins, supporting the hypothesis that the more stable proteome of the naked mole-rat contributes to its longevity.

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Seeing cells through silicon microfluidic devices

October 3, 2013

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Schematic of the lab-on-chip system for the study of
mechanical, chemical, and electric perturbation of different types of cells
on silicon-based microfluidic and multi-electrode array platform.
Quantitative phase image (through silicon) of a human embryonic kidney cell and red blood cell is shown on the top. (Credit: B. Joshi et al./Scientific Reports)

Scientists at MIT and the University of Texas at Arlington (UTA) have developed a new type of microscopy that can image cells through a silicon wafer, allowing them to precisely measure the size and mechanical behavior of cells behind the wafer.
The new technology, which relies on near-infrared light, could help scientists learn more about diseased or infected cells as they flow through silicon microfluidic devices.
“This has the potential to merge research in cellular visualization with all the exciting things you can do on a silicon wafer,” says Ishan Barman, a former postdoc in MIT’s Laser Biomedical Research Center (LBRC) and one of the lead authors of a paper describing the technology in the Oct. 2 issue of the journal Scientific Reports (open access).
The senior author is Samarendra Mohanty, an assistant professor of physics at UTA.
Silicon is commonly used to build “lab-on-a-chip” microfluidic devices, which can sort and analyze cells based on their molecular properties. Such devices have many potential applications in research and diagnostics, but they could be even more useful if scientists could image the cells inside the devices, says Barman, who is now an assistant professor of mechanical engineering at Johns Hopkins University.
To achieve that, Barman and colleagues took advantage of the fact that silicon is transparent to infrared and near-infrared wavelengths of light. They adapted a microscopy technique known as quantitative phase imaging, which works by sending a laser beam through a sample, then splitting the beam into two. By recombining those two beams and comparing the information carried by each one, the researchers can determine the sample’s height and its refractive index — a measure of how much the material forces light to bend as it passes through.
Traditional quantitative phase imaging uses a helium neon laser, which produces visible light, but for the new system the researchers used a titanium sapphire laser that can be tuned to infrared and near-infrared wavelengths (they found that light with a wavelength of 980 nanometers worked best).
Using this system, the researchers measured changes in the height of red blood cells, with nanoscale sensitivity, through a silicon wafer similar to those used in most electronics labs.
Examples of uses:

As red blood cells flow through the body, they often have to squeeze through very narrow vessels. When these cells are infected with malaria, they lose this ability to deform, and form clogs in tiny vessels. The new microscopy technique could help scientists study how this happens, the researchers say. It could also be used to study the dynamics of the malformed blood cells that cause sickle cell anemia.
The researchers also used their new system to monitor human embryonic kidney cells as pure water was added to their environment — a shock that forces the cells to absorb water and swell up. The researchers were able to measure how much the cells distended and calculate the change in their index of refraction.
Mohanty’s lab at UTA is now using the system to study how neurons grown on a silicon wafer communicate with each other.

“Nobody has shown this kind of microscopy of cellular structures before through a silicon substrate,” Mohanty says.
“This is an exciting new direction that is likely to open up enormous opportunities for quantitative phase imaging,” says Gabriel Popescu, an assistant professor of electrical engineering and computer science at the University of Illinois at Urbana-Champaign who was not part of the research team. “The possibilities are endless: From micro- and nanofluidic devices to structured substrates, the devices could target applications ranging from molecular sensing to whole-cell characterization and drug screening in cell populations,” he says.
In the Scientific Reports paper, the researchers used silicon wafers that were about 150 to 200 microns thick, but they have since shown that thicker silicon can be used if the wavelength of light is increased into the infrared range. The researchers are also working on modifying the system so that it can image in three dimensions, similar to a CT scan.
Other lead authors of the paper are former MIT postdoc Narahara Chari Dingari and UTA graduate students Bipin Joshi and Nelson Cardenas. Other authors are former MIT postdoc Jaqueline Soares, currently an assistant professor at Federal University of Ouro Preto, Brazil, and Ramachandra Rao Dasari, associate director of the LBRC.
The research was funded by the National Institute of Biomedical Imaging and Bioengineering and Nanoscope Technologies, LLC.
Department of Chemistry
“MIT shows how blood cells change shape”

Abstract for Scientific Reports paper
We report a novel technique for label-free, rapid visualization of structure and dynamics of live cells with nanoscale sensitivity through traditionally opaque media. Specifically, by combining principles of near-infrared (NIR) spectroscopy and quantitative phase imaging, functional characterization of cellular structure and dynamics through silicon substrates is realized in our study. We demonstrate the efficacy of the new approach by full-field imaging of erythrocyte morphology in their native states with a nm path length sensitivity. Additionally, we observe dynamic variations of human embryonic kidney cells, through a silicon substrate, in response to hypotonic stimulation with ms temporal resolution that also provides unique insight into the underlying biophysical changes. The proposed technology is fundamentally suited for high-performance investigations of biological specimens and significantly expands the options for visualization in complex microfluidic devices fabricated on silicon.

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Is ‘massive open online research’ (MOOR) the next frontier for education?

"The goal of this class is to make you fall in love with bioinformatics" --- Prof. Pavel Pevzner

October 3, 2013

UC San Diego is launching the first major online course that prominently features “massive open online research” (MOOR).
In “Bioinformatics Algorithms — Part 1,” UC San Diego computer science and engineering professor Pavel Pevzner and his graduate students are offering a course on Coursera that combines research with a MOOC (massive open online course) for the first time.
“All students who sign up for the course will be given an opportunity to work on specific research projects under the leadership of prominent bioinformatics scientists from different countries, who have agreed to interact and mentor their respective teams.”
“The natural progression of education is for people to make a transition from learning to research, which is a huge jump for many students, and essentially impossible for students in isolated areas,” said Ph.D. student Phillip Compeau, who helped develop the online course. “By integrating the research with an interactive text and a MOOC, it creates a pipeline to streamline this transition.”
Bioinformatics Algorithms (Part I) will run for eight weeks starting October 21, and students are now able to sign up and download some of the course materials. It is offered free of charge to everyone.
Book, content delivery system

Bioinformatics Algorithms (Part 1) (credit: UCSD/Coursera)

Another unique feature of the online course: Pevzner and Compeau have developed Bioinformatics Algorithms: An Active-Learning Approach, a e-book supporting the course, while Pevzner’s colleagues in Russia developed a content delivery system that integrates the e-book with hundreds of quizzes and dozens of homework problems.
The U.S.-Russian team, led by Pevzner’s foreign student Nikolay Vyahhi, also implemented the online course using the beta version of Stepic, a new, fully integrated educational platform and startup developed by Vyahhi. (Stepic derives its name from the “step-by-step, epic” solution its developers delivered for electronic publishing.)
The course also provides access to Rosalind, a free online resource for learning bioinformatics through problem solving. Rosalind was developed by Pevzner’s students and colleagues in San Diego and St. Petersburg with funding from the Howard Hughes Medical Institute, the Russian Ministry of Education, and Russian Internet billionaires Yuri Milner and Pavel Durov through their “Start Fellows” award. Rosalind already has over 10,000 active users worldwide.
Rosalind — named in honor of British scientist Rosalind Franklin, whose X-ray crystallography with Raymond Gosling facilitated the discovery of the DNA double helix by Watson and Crick — will grade the programming assignments. They come in the form of bioinformatics problems of growing complexity as the course progresses.
“We developed Rosalind to inspire both biologists and computer science students,” said Rosalind principal developer Vyahhi, who worked with Pevzner during the latter’s sabbatical in Russia. “The platform allows biologists to develop vital programming skills for bioinformatics at their own pace, and Rosalind can also appeal to programmers who have never been exposed to some of the exciting computational problems generated by molecular biology.”
“We have already started testing the first modules of the Bioinformatics Algorithms course in top Russian universities,” said Pevzner. “We are getting good feedback, and we hope to reach out to early students registering for the Coursera course so we can perform a ‘stress’ test — just to make sure that we will be able to deliver on the promise of massive open online research projects, whether it’s hundreds or thousands of students who enroll.”
The UC San Diego course, produced in Calit2’s Qualcomm Institute at UC San Diego, will cover many algorithms underlying fundamental topics in bioinformatics and will try to answer questions like, “What DNA Patterns Play the Role of Molecular Clocks Inside Cells,” or, “How Have Humans Populated the Earth?” To answer these questions, Pevzner and his team will introduce fundamental computational concepts such as greedy and randomized algorithms, graph theory and combinatorics, dynamic programming and combinatorial pattern matching, and many others.
‘We want you to switch to bioinformatics’
“Whatever you are studying now — computer science, biology, or mathematics — we want you to switch to bioinformatics,” exhorted Pevzner in the promotional video. “Not because these disciplines are not important, quite the opposite; but because bioinformatics is so cool, and because it is built on all of these disciplines!”
Pevzner was working on his Ph.D. in discrete mathematics when he had his first encounter with bioinformatics, and he says that he started over in the “futuristic new discipline — and never looked back.” He is now a professor of Computer Science and Engineering at UC San Diego, where he holds the Ronald R. Taylor Chair.
In 2006, Pevzner was named a Howard Hughes Medical Institute Professor. His research has focused on the creation of bioinformatics algorithms for analyzing genome rearrangements, DNA sequencing, and computational proteomics. He is a Fellow of both the Association for Computing Machinery (ACM) and the International Society for Computational Biology (ISCB).
In 2011, Pevzner founded the Algorithmic Biology Laboratory in St. Petersburg, Russia, which develops the Rosalind bioinformatics platform.
Topping a long list of publications, Pevzner authored Computational Molecular Biology (The MIT Press, 2000), co-authored (jointly with Neil Jones) An Introduction to Bioinformatics Algorithms (The MIT Press, 2004), and co-edited (with Ron Shamir) Bioinformatics for Biologists (Cambridge University Press, 2011).
But asked about which book makes him most proud — and Pevzner is unequivocal. “Absolutely this new book for the Bioinformatics Algorithms course,” he said. “Thanks to Coursera and the online learning explosion, we have the opportunity to reach many more students than would be possible at one university or even one country. There are students everywhere who could use this as a stepping stone to a career in a field that is going to change the world as we know it. Who wouldn’t want to be a part of that?”

Wednesday, October 2, 2013

New programming language directs DNA to build custom-designed molecules

October 2, 2013

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An example of a chemical program. Here, A, B and C are different chemical species. (Credit: Yan Liang/L2XY2.com)

A team led by the University of Washington has developed a programming language to help design chemical-reaction networks (equations that describes how mixtures of chemicals behave).
The objective is to control how DNA molecules build custom-designed molecules in a test tube or cell, which could serve as “smart” drug deliverers or disease detectors at the cellular level, for example.
“We start from an abstract mathematical description of a chemical system, and then use DNA to build the molecules that realize the desired dynamics,” said corresponding author Georg Seelig, a UW assistant professor of electrical engineering and of computer science and engineering.
Currently, when a biologist or chemist makes a certain type of molecular network, the engineering process is complex, cumbersome and hard to repurpose for building other systems.
“I think this is appealing because it allows you to solve more than one problem,” Seelig said. “If you want a computer to do something else, you just reprogram it. This project is very similar in that we can tell chemistry what to do.”
Humans and other organisms already have complex networks of nano-sized molecules that help to regulate cells and keep the body in check. Scientists now are finding ways to design synthetic systems that behave like biological ones with the hope that synthetic molecules could support the body’s natural functions. To that end, a system is needed to create synthetic DNA molecules that vary according to their specific functions.

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Nucleic acid nanocontroller. A standardized signaling protocol based on short single strands of DNA enables the components of the nanocontroller to communicate with each other. The formalism of chemical-reaction networks serves as a programming language that specifies the desired behavior for the computational subsystem. The target behavior is experimentally realized by the DNA architecture. (Credit: Yuan-Jyue Chen et al., Nature Nanotechnology)

The new approach isn’t ready to be applied in the medical field, but future uses could include using this framework to make molecules that self-assemble within cells and serve as “smart” sensors. These could be embedded in a cell, then programmed to detect abnormalities and respond as needed, perhaps by delivering drugs directly to those cells.
Seelig and colleague Eric Klavins, a UW associate professor of electrical engineering, recently received $2 million from the National Science Foundation as part of a national initiative to boost research in molecular programming. The new language will be used to support that larger initiative, Seelig said. The research was also funded by the Burroughs Wellcome Fund and the National Centers for Systems Biology.
California Institute of Technology; Microsoft Research, and University of California, San Francisco researchers were co-authors of the study.

Abstract of Nature Nanotechnology paper:
Biological organisms use complex molecular networks to navigate their environment and regulate their internal state. The development of synthetic systems with similar capabilities could lead to applications such as smart therapeutics or fabrication methods based on self-organization. To achieve this, molecular control circuits need to be engineered to perform integrated sensing, computation and actuation. Here we report a DNA-based technology for implementing the computational core of such controllers. We use the formalism of chemical reaction networks as a ’programming language’ and our DNA architecture can, in principle, implement any behaviour that can be mathematically expressed as such. Unlike logic circuits, our formulation naturally allows complex signal processing of intrinsically analogue biological and chemical inputs. Controller components can be derived from biologically synthesized (plasmid) DNA, which reduces errors associated with chemically synthesized DNA. We implement several building-block reaction types and then combine them into a network that realizes, at the molecular level, an algorithm used in distributed control systems for achieving consensus between multiple agents.

(¯`*• Global Source and/or more resources at http://goo.gl/zvSV7 │ www.Future-Observatory.blogspot.com and on LinkeIn Group's "Becoming Aware of the Futures" at http://goo.gl/8qKBbK │ @SciCzar │ Point of Contact: www.linkedin.com/in/AndresAgostini

Why glial cells should be included in the BRAIN initative

October 2, 2013

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23 week fetal brain culture astrocyte, a type of glial cell (credit: Wikimedia Commons)

Glia, the non-neuronal cells that make up most of the brain, must not be left out of the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, says R. Douglas Fields, chief of the Nervous System Development and Plasticity Section at NIH, in Nature News.
“A major stumbling block is the project’s failure to consider that although the human brain contains roughly 100 billion neurons, it contains billions more non-electrical brain cells called glia,” he said.
“These reside outside the neuronal “connectome” and operate beyond the reach of tools designed to probe electrical signaling in neurons. Dismissed as connective tissue when they were first described in the mid-1800s, glia have long been neglected in the quest to understand neuronal signalling. …
“Research is revealing that glia can sense neuronal activity and control it. Various studies also indicate that glia operate in diverse mental processes, for instance, in the formation of memories. They have a central role in brain injury and disease, and they are even at the root of various disorders — such as schizophrenia and Alzheimer’s — previously presumed to be exclusively neuronal. …
“When experts on neuronal plasticity and computational neuroscience came together with glial experts at a workshop in February entitled Glial Biology in Learning and Cognition, held at the US National Science Foundation in Arlington, Virginia, our unanimous conclusion was that neurons working alone provide only a partial explanation for complex cognitive processes, such as the formation of memories.
“The complex branching structure of glial cells and their relatively slow chemical (as opposed to electrical) signalling in fact make them better suited than neurons to certain cognitive processes. These include processes requiring the integration of information from spatially distinct parts of the brain, such as learning or the experiencing of emotions, which take place over hours, days and weeks, not in milliseconds or seconds.”

(¯`*• Global Source and/or more resources at http://goo.gl/zvSV7 │ www.Future-Observatory.blogspot.com and on LinkeIn Group's "Becoming Aware of the Futures" at http://goo.gl/8qKBbK │ @SciCzar │ Point of Contact: www.linkedin.com/in/AndresAgostini

Why don’t we have fusion yet?

October 2, 2013

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The preamplifiers of the National Ignition Facility. The unified lasers deliver 1.8 megajoules of energy and 500 terawatts of power — 1,000 times more than the United States uses at any one moment. (Credit: Damien Jemison/LLNL)

The dream of igniting a self-sustained fusion reaction with high yields of energy, a feat likened to creating a miniature star on Earth, is getting closer to becoming reality, according the authors of a new review article in the journal Physics of Plasmas.
Researchers at the National Ignition Facility (NIF) report that while there is at least one significant obstacle to overcome before achieving the highly stable precisely directed implosion required for ignition, they have met many of the demanding challenges leading up to that goal since experiments began in 2010.
To reach ignition (defined as the point at which the fusion reaction produces more energy than is needed to initiate it), the NIF focuses 192 laser beams simultaneously in billionth-of-a-second pulses inside a cryogenically cooled hohlraum (from the German word for “hollow room”), a hollow cylinder the size of a pencil eraser.
Within the hohlraum is a ball-bearing-size capsule containing two hydrogen isotopes, deuterium and tritium (D-T). The unified lasers deliver 1.8 megajoules of energy and 500 terawatts of power — 1,000 times more than the United States uses at any one moment — to the hohlraum, creating an “X-ray oven” that implodes the D-T capsule to temperatures and pressures similar to those found at the center of the sun.
“What we want to do is use the X-rays to blast away the outer layer of the capsule in a very controlled manner.
That’s so the D-T pellet is compressed to just the right conditions to initiate the fusion reaction,” explained John Edwards, NIF associate director for inertial confinement fusion and high-energy-density science.
One major hurdle

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Schematic of NIF ignition target and capsule (credit: M. J. Edwards et al., Physics of Plasmas)

“In our new review article, we report that the NIF has met many of the requirements believed necessary to achieve ignition — sufficient X-ray intensity in the hohlraum, accurate energy delivery to the target and desired levels of compression — but that at least one major hurdle remains to be overcome: the premature breaking apart of the capsule.”
In the article, Edwards and his colleagues discuss how they are using diagnostic tools developed at NIF to determine likely causes for the problem. “In some ignition tests, we measured the scattering of neutrons released and found different strength signals at different spots around the D-T capsule,” Edwards said.
“This indicates that the shell’s surface is not uniformly smooth and that in some places, it’s thinner and weaker than in others. In other tests, the spectrum of X-rays emitted indicated that the D-T fuel and capsule were mixing too much — the results of hydrodynamic instability — and that can quench the ignition process.”
Edwards said that the team is concentrating its efforts on NIF to define the exact nature of the instability and use the knowledge gained to design an improved, sturdier capsule. Achieving that milestone, he said, should clear the path for further advances toward laboratory ignition.
The project is led by the Department of Energy’s Lawrence Livermore National Laboratory and includes partners from the University of Rochester’s Laboratory for Laser Energetics, General Atomics, Los Alamos National Laboratory, Sandia National Laboratory, and the Massachusetts Institute of Technology.
The article, “Progress toward ignition on the National Ignition Facility” by M.J. Edwards et al. appears in the journal Physics of Plasmas. Authors of this paper are affiliated with Lawrence Livermore National Laboratory, General Atomics in San Diego, Calif., the Massachusetts Institute of Technology, the University of Rochester, Los Alamos National Laboratory, and Sandia National Laboratory.
Physics of Plasmas, produced by AIP Publishing with the cooperation of the American Physical Society (APS) Division of Plasma Physics, is devoted to original experimental and theoretical contributions to the physics of plasmas.

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Extending MRI to nanoscale resolution

October 2, 2013

[+]

Illustration of the experimental setup shows the two unique components of the team’s novel MRI technique that was successful in producing a 2D MRI image with spatial resolution on the nanoscale (credit: Budakian et al./University of Illinois at Urbana-Champaign)

University of Illinois at Urbana-Champaign and Northwestern University researchers have devised a novel nuclear magnetic resonance imaging (MRI) technique that delivers about 10 nanometers spatial resolution.
This represents a significant advance in MRI sensitivity. Current MRI techniques commonly used in medical imaging yield spatial resolutions on the millimeter length scale, with the highest-resolution experimental instruments giving spatial resolution of a few micrometers.
“Our approach brings MRI one step closer in its eventual progress toward atomic-scale imaging,” said U. of I. physicist Raffi Budakian, who led the research effort.
The new breakthrough technique introduces two unique components to overcome obstacles to applying classic pulsed magnetic resonance techniques in nanoscale systems:

A novel protocol for spin manipulation applies periodic radio-frequency magnetic field pulses to encode temporal correlations in the statistical polarization of nuclear spins in the sample.
A nanoscale metal constriction focuses current, generating intense magnetic-field pulses.

In their proof-of-principle demonstration, the team used an ultrasensitive magnetic resonance sensor based on a silicon nanowire oscillator to reconstruct a two-dimensional projection image of the proton density in a polystyrene sample at nanoscale spatial resolution.
“We expect this new technique to become a paradigm for nanoscale magnetic-resonance imaging and spectroscopy into the future,” added Budakian. “It is compatible with and can be incorporated into existing conventional MRI technologies.”
Exclusive KurzweilAI interview with Prof. Budakian
What are the major applications of your research and when can we expect to see operational devices?
Specifically, we are focused on imaging biological systems between 1–100 nm. These include proteins and viruses. MRI is a powerful tool for studying biological systems because it offers a host of unique modalities for imaging. It is nondestructive, fully three-dimensional, and chemically specific. Extending these capabilities to the nanometer scale would, among other things, transform our understanding of protein structure, which would enable more effective drug development. Our approach would permit the application of established techniques in clinical MRI to the nanometer scale.
We are in the beginning stages of this new technology. We need several more years of technique development before we can apply this technique to answer biologically relevant questions. Of course, the speed of progress depends a great deal on the funding situation. The application of this technique will not be in a clinical setting. I have not approached any commercial companies with this idea. It’s still very new.
What is the highest resolution available in current MRI devices and how do they compare with your work?
The highest resolution inductively-coupled MRI measurements that I am aware of is 3.7 x 3.3 x 3.3 micrometers [2]. There is a number of people in the force-detected MRI community working on developing nanoscale MRI.. There is also a growing community of people trying to apply nitrogen vacancy centers to nanoscale MRI [3,4].
The first work that demonstrated nanoscale MRI imaging was by Degan et al.[5]. Like the previous work, our approach uses force-detected magnetic resonance imaging. Our approach differs in several important aspects to that work. One of the most significant differences is the use of time-dependent magnetic field gradients for spin detection and imaging. The ability to control the time dependence of the magnetic fields permits the use of all other pulsed magnetic resonance techniques for nanoscale imaging and spectroscopy.
What are your plans for future development?
The goal of our work is to extend the capabilities of MRI to the nanometer scale. In this initial proof-of-concept work, we demonstrated 10-nm spatial resolution imaging of proton spins in polystyrene. In the next 2–3 years, our goal is to demonstrate proton spin imaging in biological systems with 1–3 nm spatial resolution.

Abstract of Physical Review X paper [1]

We report a method for nanometer-scale pulsed nuclear magnetic resonance imaging and spectroscopy. Periodic radio-frequency pulses are used to create temporal correlations in the statistical polarization of a solid organic sample. The spin density is spatially encoded by applying a series of intense magnetic field gradient pulses generated by focusing electric current through a nanometer-scale metal constriction. We demonstrate this technique using a silicon nanowire mechanical oscillator as a magnetic resonance sensor to image ¹H spins in a polystyrene sample. We obtain a two-dimensional projection of the sample proton density with approximately 10-nm resolution.

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Tuesday, October 1, 2013

How to make ceramics that bend without breaking

New materials developed at MIT could lead to actuators on a chip and self-deploying medical devices

October 1, 2013

[+]

When subjected to a load, the molecular structure of a zirconia ceramic material (austenite) deforms (in its martensite phase) rather than cracking,. When heated, it then returns to its original shape. (Credit: Lai et al./MIT)

Ceramics tend to crack under stress. But researchers from MIT and Nanyang Technological University in Singapore have developed a way of making minuscule flexible ceramic objects that also have a “memory” for shape (when bent and then heated, they return to their original shapes).
The surprising discovery is reported this week in the journal Science, in a paper by MIT graduate student Alan Lai, professor Christopher Schuh, and two collaborators in Singapore.
Shape-memory materials, which can bend and then snap back to their original configurations in response to a temperature change, have been known since the 1950s in metals, and some polymers, but not in ceramics,” explains Schuh, the Danae and Vasilis Salapatas Professor of Metallurgy and head of MIT’s Department of Materials Science and Engineering.
The team accomplished this in two key ways.

Created tiny ceramic objects, invisible to the naked eye: “When you make things small, they are more resistant to cracking,” Schuh says.
Made the individual crystal grains span the entire small-scale structure, removing the crystal-grain boundaries where cracks are most likely to occur.

Those tactics resulted in tiny samples of ceramic material with deformability equivalent to about 7 percent of their size. “Usually if you bend a ceramic by 1 percent, it will shatter,” Schuh says. But these tiny filaments, with a diameter of just 1 micrometer — one millionth of a meter — can be bent by 7 to 8 percent repeatedly without any cracking, he says.
Ceramic-like strength, but metal-like ductility
These materials could be important tools for those developing micro- and nanodevices, such as for biomedical applications, Schuh says, such as microactuators to trigger actions within such devices — the release of drugs from tiny implants, for example.
Compared to the materials currently used in microactuators, Schuh says, the strength of the ceramic would allow it to exert a stronger push in a microdevice.
The ceramics used in this research were made of zirconia, but the same techniques should apply to other ceramic materials. Zirconia is “one of the most well-studied ceramics,” Lai says, and is already widely used in engineering. It is also used in fuel cells, considered a promising means of providing power for cars, homes and even for the electric grid. While there would be no need for elasticity in such applications, the material’s flexibility could make it more resistant to damage.
The material combines some of the best attributes of metals and ceramics, the researchers say: Metals have lower strength but are very deformable, while ceramics have much greater strength, but almost no ductility — the ability to bend or stretch without breaking. The newly developed ceramics, Schuh says, have “ceramic-like strength, but metal-like ductility.”

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NASA space telescopes find patchy clouds on exotic world

October 1, 2013

Kepler-7b (left), which is 1.5 times the radius of Jupiter (right), is the first exoplanet to have its clouds mapped. This artist’s concept shows what those clouds might look like. The cloud map was produced using data from NASA’s Kepler and Spitzer space telescopes. The map shows that clouds cover the western side of the gaseous planet, leaving the east cloud-free. Researchers speculate the clouds are made up of minerals containing silicates. Kepler-7b is one of the puffiest, or least dense, planets known. While it is 1.5 times the size of Jupiter is has only about half the mass. (Credit: NASA/JPL-Caltech/MIT)

Astronomers using data from NASA’s Kepler and Spitzer space telescopes have created the first cloud map of a planet beyond our solar system: a sizzling, Jupiter-like world known as Kepler-7b.
The planet is marked by high clouds in the west and clear skies in the east. Previous studies from Spitzer have resulted in temperature maps of planets orbiting other stars, but this is the first look at cloud structures on a distant world.
“By observing this planet with Spitzer and Kepler for more than three years, we were able to produce a very low-resolution ‘map’ of this giant, gaseous planet,” said Brice-Olivier Demory of MIT. Demory is lead author of a paper accepted for publication in the Astrophysical Journal Letters. “We wouldn’t expect to see oceans or continents on this type of world, but we detected a clear, reflective signature that we interpreted as clouds.”
Kepler has discovered more than 150 exoplanets, which are planets outside our solar system, and Kepler-7b was one of the first. The telescope’s problematic reaction wheels prevent it from hunting planets any more, but astronomers continue to pore over almost four years’ worth of collected data.
Kepler’s visible-light observations of Kepler-7b’s moon-like phases led to a rough map of the planet that showed a bright spot on its western hemisphere. But these data were not enough on their own to decipher whether the bright spot was coming from clouds or heat. The Spitzer Space Telescope played a crucial role in answering this question.
Like Kepler, Spitzer can fix its gaze at a star system as a planet orbits around the star, gathering clues about the planet’s atmosphere. Spitzer’s ability to detect infrared light means it was able to measure Kepler-7b’s temperature, estimating it to be between 1,500 and 1,800 degrees Fahrenheit (1,100 and 1,300 Kelvin).
This is relatively cool for a planet that orbits so close to its star — within 0.06 astronomical units (one astronomical unit is the distance from Earth and the sun) — and, according to astronomers, too cool to be the source of light Kepler observed. Instead, they determined, light from the planet’s star is bouncing off cloud tops located on the west side of the planet.
“Kepler-7b reflects much more light than most giant planets we’ve found, which we attribute to clouds in the upper atmosphere,” said Thomas Barclay, Kepler scientist at NASA’s Ames Research Center in Moffett Field, Calif. “Unlike those on Earth, the cloud patterns on this planet do not seem to change much over time — it has a remarkably stable climate.”
A new tool for studying exoplanets similar to Earth
The findings are an early step toward using similar techniques to study the atmospheres of planets more like Earth in composition and size.
“With Spitzer and Kepler together, we have a multi-wavelength tool for getting a good look at planets that are trillions of miles away,” said Paul Hertz, director of NASA’s Astrophysics Division in Washington. “We’re at a point now in exoplanet science where we are moving beyond just detecting exoplanets, and into the exciting science of understanding them.”
Kepler identified planets by watching for dips in starlight that occur as the planets transit, or pass in front of their stars, blocking the light. This technique and other observations of Kepler-7b previously revealed that it is one of the puffiest planets known: if it could somehow be placed in a tub of water, it would float. The planet was also found to whip around its star in just less than five days.
Explore all 900-plus exoplanet discoveries with NASA’s “Eyes on Exoplanets,” a fully rendered 3D visualization tool, available for download. The program is updated daily with the latest findings from NASA’s Kepler mission and ground-based observatories around the world as they search for planets like our own.
University of California, Santa Cruz, California Institute of Technology, the University of Bern, Yale University, the University of Liège, the French National Center for Scientific Research, and Northwestern University were also involved in the research.

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NASA wants investigations for a Mars 2020 rover

October 1, 2013

Planning for NASA’s 2020 Mars rover envisions a basic structure that capitalizes on the design and engineering work done for the NASA rover Curiosity, which landed on Mars in 2012, but with new science instruments selected through competition for accomplishing different science objectives (credit: NASA/JPL-Caltech)

NASA has announced an open competition for the planetary community to submit proposals for the science and exploration technology instruments that would be carried aboard the agency’s next Mars rover, scheduled for launch in July/August of 2020.
The Mars 2020 rover will explore and assess Mars as a potential habitat for life, search for signs of past life, collect carefully selected samples for possible future return to Earth, and demonstrate technology for future human exploration of the Red Planet.
Officially called the Mars 2020 Mission Investigations Announcement of Opportunity (AO), this competition solicits flight investigations for which each principal investigator or scientist is responsible for a complete space flight investigation, including instrument hardware, mission operations and data analysis. T
he total allocated cost for development of all the investigations selected and funded by NASA is approximately $130 million.
The competitively selected instruments will be placed on a rover similar to Curiosity, which landed on Mars in August 2012. Using Curiosity’s design will help minimize mission costs and risks and deliver a rover that can accomplish the mission objectives. The Mars 2020 mission also would build upon the scientific accomplishments of Curiosity and other previous Mars missions.
What’s different about Mars 2020
In January 2013, NASA appointed a Science Definition Team to outline objectives for the Mars 2020 mission. The team, composed of 19 scientists and engineers from universities and research organizations, proposed a mission concept that could accomplish several high-priority planetary science goals and be a major step in meeting President Obama’s challenge to send humans to Mars in the 2030s.
According to the Science Definition Team, looking for signs of past life is the next logical step.
“The Mars 2020 mission will provide a unique capability to address the major questions of habitability and life in the solar system,” said Jim Green, director of NASA’s Planetary Science Division in Washington. “The science conducted by the rover’s instruments also would expand our knowledge of Mars and provide the context needed to make wise decisions about whether to return any collected samples to Earth.”
This rover will make measurements of mineralogy and rock chemistry down to a microscopic scale, so that we might be able to understand the Martian environment surrounding the rover’s landing site and identify evidence of possible past life.
The 2020 rover could also make measurements and conduct technology demonstrations to help designers of a human expedition understand any hazards posed by Martian dust and demonstrate how to collect carbon dioxide, which could be a resource for making oxygen and rocket fuel.
“The Mars 2020 rover will test technologies that are key to one-day landing human explorers on the Red Planet,” said Jason Crusan, director of NASA’s Advanced Exploration Systems Division. “New technologies could allow astronauts to live off the land as they explore the ancient valleys of Mars. The capability to manufacture breathable air, rocket fuel, water and more may forever change how we explore space.”

A hidden genetic code for better designer genes

How rare "words" in bacterial genes boost protein production

October 1, 2013

Wyss Institute scientists synthesized 14,000 snippets of DNA (individual pixels) and tested how well they promote protein synthesis. They found that those with rare ³words² (codons) near the start of bacterial genes made more protein (green pixels) by removing roadblocks to protein production. (Credit: Wyss Institute)

Scientists routinely seek to reprogram bacteria to produce proteins for drugs, biofuels and more, but they have struggled to get those bacteria to follow orders.
A hidden feature of the genetic code, it turns out, could achieve that. The feature controls how much of the desired protein bacteria produce, a team from the Wyss Institute for Biologically Inspired Engineering at Harvard University reported in the September 26 online issue of Science.
Rare condons
The researchers combined high-speed “next-generation” DNA sequencing and DNA synthesis technologies and found that using more rare words, or codons, near the start of a gene removes roadblocks to protein production.
The research team is headed by Sri Kosuri, Ph.D., a Wyss Institute staff scientist, George Church, Ph.D., a core faculty member at the Wyss Institute and professor of genetics at Harvard Medical School, and Daniel Goodman, a Wyss Institute graduate research fellow,
“Now that we understand how rare codons control gene expression, we can better predict how to synthesize genes that make enzymes, drugs, or whatever you want to make in a cell,” Kosuri said.
The findings could be a boon for biotechnologists,and could help synthetic biologists reprogram bacteria to make new drugs and biological devices.
To produce a protein, a cell must first make working copies of the gene encoding it. These copies, called messenger RNA (mRNA), consist of a specific string of words, or codons. Each codon represents one of the 20 different amino acids that cells use to assemble proteins. But since the cell uses 61 codons to represent 20 amino acids, many codons have synonyms that represent the same amino acid.
In bacteria, as in books, some words are used more often than others, and molecular biologists have noticed over the last few years that rare codons appear more frequently near the start of a gene. What’s more, genes whose opening sequences have more rare codons produce more protein than genes whose opening sequences do not.
No one knew for sure why rare codons had these effects, but many biologists suspected that they function as a highway on-ramp for ribosomes, the molecular machines that build proteins. According to this idea, called the codon ramp hypothesis, ribosomes wait on the on-ramp, then accelerate slowly along the mRNA highway, allowing the cell to make proteins with all deliberate speed.
But without the on-ramp, the ribosomes gun it down the mRNA highway, then collide like bumper cars, causing traffic accidents that slow protein production. Other biologists suspected rare codons acted via different mechanisms. These include mRNA folding, which could create roadblocks for ribosomes that block the highway and slow protein production.
A high-speed, multiplexed method
To see which ideas were correct, the three researchers used a high-speed, multiplexed method that they’d reported in August in The Proceedings of the National Academy of Sciences.
First, they tested how well rare codons activate genes by mass-producing 14,000 snippets of DNA with either common or rare codons; splicing them near the start of a gene that makes cells glow green, and inserting each of those hybrid genes into different bacteria. Then they grew those bugs, sorted them into bins based on how intensely they glowed, and sequenced the snippets to look for rare codons.
They found that genes that opened with rare codons consistently made more protein, and a single codon change could spur cells to make 60 times more protein.
“That’s a big deal for the cell, especially if you want to pump out a lot of the protein you’re making,” Goodman said.
The results were also consistent with the codon-ramp hypothesis, which predicts that rare codons themselves, rather than folded mRNA, slow protein production. But the researchers also found that the more mRNA folded, the less of the corresponding protein it produced — a result that undermined the hypothesis.
To put the hypothesis to a definitive test, the Wyss team made and tested more than 14,000 mRNAs — including some with rare codons that didn’t fold well, and others that folded well but had no rare codons. By quickly measuring protein production from each mRNA and analyzing the results statistically, they could separate the two effects.
The results showed clearly that RNA folding, not rare codons, controlled protein production, and that scientists can increase protein production by altering folding, Goodman said.
The new method could help resolve other thorny debates in molecular biology. “The combination of high-throughput synthesis and next-gen sequencing allows us to answer big, complicated questions that were previously impossible to tease apart,” Church said.
“These findings on codon use could help scientists engineer bacteria more precisely than ever before, which is tremendous in itself, and they provide a way to greatly increase the efficiency of microbial manufacturing, which could have huge commercial value as well,” said Wyss Institute Founding Director Don Ingber, M.D., Ph.D. “They also underscore the incredible value of the new automated technologies that have emerged from the Synthetic Biology Platform that George leads, which enable us to synthesize and analyze genes more rapidly than ever before.”
The work was funded by the Department of Energy, the Office of Naval Research, Agilent Technologies, an NSF Graduate Research Fellowship to Daniel Goodman, and the Wyss Institute.

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Human on a chip

October 1, 2013

(Credit: U.S. Army)

Army scientists at the Edgewood Chemical Biological Center (ECBC) and academic collaborators are conducting research on organoids (small swatches of human tissue) on microchips.
The “human on a chip” research focuses on in vitro human organ constructs (for the heart, liver, lung and the circulatory system) in communication with each other. The goal is to assess effectiveness and toxicity of drugs in a way that is relevant to humans and their ability to process these drugs.
“The screening models will be used to assess the efficacy and safety of medical mitigation procedures and countermeasures for the soldier and the nation as a whole,” said Dr. Harry Salem, ECBC’s chief scientist for Life Sciences.
Each organ-on-a-chip is about the size of a thumb drive and is an “organoid” (a structure that resembles an organ in appearance or function), designed to mimic the properties of an actual human organ.
The organoids are created by induced pluripotent stem cells made from adult skin cells. They comprise multiple layers of cells growing on a membrane, connected to each other by microfluidics (tiny micro channels) that copy the function of blood vessels.
Their primary purpose is to take the place of animal research. According to Salem, compounds quite often behave differently in people than they do in animals. For that reason, human-estimate studies are used, but do not always accurately reflect the human response. Due to the species-specific differences by which compounds are metabolized, a drug tested on a laboratory rat doesn’t always translate well to a human.
In some cases, no animal testing can mimic the human response. Asthma, for example, is a uniquely human disease. Since human-on-a-chip is made from human cells, it is the next best thing. Human tissue reacts like human tissue.
New predictive models of toxicity
The researchers anticipate that new predictive models of toxicity will result from the more accurate human-on-a-chip testing, saving time and money. Pharmaceuticals tested on animals fail to work on humans 90 percent of the time. This technology will result in fewer test failures. Scientists will be able to narrow their research efforts by identifying which therapeutics will be effective or fail early on in the testing process, the researchers say.
The center houses the only laboratories in the United States that the Chemical Weapons Convention permits to produce chemical warfare agent for testing purposes. ECBC will test the human-on-a-chip against chemical warfare agents to learn more about how the body will respond to agent exposure and explore various treatment options for exposures.
“The human-on-a-chip promises to accelerate the pace of research and consequently scientific breakthroughs,” Dr. Russell Dorsey, a research microbiologist and one of the members performing the in vitro testing at ECBC, said. “For the military, our human-on-a-chip research will save actual warfighters’ lives.”
The center will be collaborating with the U.S. Army Medical Research Institute of Chemical Defense, Wake Forest, Harvard, and the University of Michigan on the chip design.
The five-year research project is funded by the Defense Threat Reduction Agency.

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Monday, September 30, 2013

Syria's War Viewed Almost in Real Time

For the first time, the war in Syria has given global audiences a close-up view of war

ORGANIZATIONS .. I HAVE WORKED WITH !

(¯`*•. As a consultant, manager and strategist, Andres has worked with institutions such as:

► Toyota,
► Mitsubishi,
► World Bank,
► Shell,
► Statoil,
► Total,
► Exxon,
► Mobil,
► Citgo,
► PDVSA,
► GE,
► GMAC,
► TNT Delivery Express,
► GTE,
► Amoco,
► BP,
► Abbot Laboratories,
► World Health Organization,
► Ernst Young Consulting,
► SAIC (Science Applications International Corporation),
► Pak Mail,
► Wilpro (Williams Company),
► Phillips Petroleum Company,
► Dupont,
► Conoco,
► ENI (Italy’s petroleum state-owned firm),
► Chevron, and
► LDG Management (HCC Benefits).

NASA's VISION-21 Symposium

The VISION-21 Symposium sponsored by NASA Lewis Research Center and the Ohio Aerospace Institute, March 30-31, 1993.

The original version of this article was presented at the VISION-21 Symposium sponsored by NASA Lewis Research Center and the Ohio Aerospace Institute, March 30-31, 1993. A slightly changed version appeared in the Winter 1993 issue of Whole Earth Review.

Vernor Vinge

Department of Mathematical Sciences

San Diego State University

(This article may be reproduced for noncommercial purposes if it is copied in its entirety, including this notice.)

Abstract

Within thirty years, we will have the technological means to create superhuman intelligence. Shortly after, the human era will be ended.

Is such progress avoidable? If not to be avoided, can events be guided so that we may survive? These questions are investigated. Some possible answers (and some further dangers) are presented.

What is The Singularity?

The acceleration of technological progress has been the central feature of this century. I argue in this paper that we are on the edge of change comparable to the rise of human life on Earth. The precise cause of this change is the imminent creation by technology of entities with greater than human intelligence.

There are several means by which science may achieve this breakthrough (and this is another reason for having confidence that the event will occur):

There may be developed computers that are "awake" and superhumanly intelligent. (To date, there has been much controversy as to whether we can create human equivalence in a machine. But if the answer is "yes, we can", then there is little doubt that beings more intelligent can be constructed shortly thereafter.)

Large computer networks (and their associated users) may "wake up" as a superhumanly intelligent entity.

Computer/human interfaces may become so intimate that users may reasonably be considered superhumanly intelligent.

Biological science may provide means to improve natural human intellect.

The first three possibilities depend in large part on improvements in computer hardware. Progress in computer hardware has followed an amazingly steady curve in the last few decades [17]. Based largely on this trend, I believe that the creation of greater than human intelligence will occur during the next thirty years. (Charles Platt [20] has pointed out that AI enthusiasts have been making claims like this for the last thirty years. Just so I'm not guilty of a relative-time ambiguity, let me more specific: I'll be surprised if this event occurs before 2005 or after 2030.)

What are the consequences of this event? When greater-than-human intelligence drives progress, that progress will be much more rapid. In fact, there seems no reason why progress itself would not involve the creation of still more intelligent entities -- on a still-shorter time scale.

The best analogy that I see is with the evolutionary past: Animals can adapt to problems and make inventions, but often no faster than natural selection can do its work -- the world acts as its own simulator in the case of natural selection. We humans have the ability to internalize the world and conduct "what if's" in our heads; we can solve many problems thousands of times faster than natural selection.

Now, by creating the means to execute those simulations at much higher speeds, we are entering a regime as radically different from our human past as we humans are from the lower animals.

From the human point of view this change will be a throwing away of all the previous rules, perhaps in the blink of an eye, an exponential runaway beyond any hope of control.

Developments that before were thought might only happen in "a million years" (if ever) will likely happen in the next century. (In [5], Greg Bear paints a picture of the major changes happening in a matter of hours.)

I think it's fair to call this event a singularity ("the Singularity" for the purposes of this paper). It is a point where our old models must be discarded and a new reality rules. As we move closer to this point, it will loom vaster and vaster over human affairs till the notion becomes a commonplace.

Yet when it finally happens it may still be a great surprise and a greater unknown. In the 1950s there were very few who saw it: Stan Ulam [28] paraphrased John von Neumann as saying:

One conversation centered on the ever accelerating progress of technology and changes in the mode of human life, which gives the appearance of approaching some essential singularity in the history of the race beyond which human affairs, as we know them, could not continue.

Von Neumann even uses the term singularity, though it appears he is thinking of normal progress, not the creation of superhuman intellect. (For me, the superhumanity is the essence of the Singularity. Without that we would get a glut of technical riches, never properly absorbed (see [25]).)

In the 1960s there was recognition of some of the implications of superhuman intelligence. I. J. Good wrote [11]:

Let an ultraintelligent machine be defined as a machine that can far surpass all the intellectual activities of any any man however clever.

Since the design of machines is one of these intellectual activities, an ultraintelligent machine could design even better machines; there would then unquestionably be an "intelligence explosion," and the intelligence of man would be left far behind.

Thus the first ultraintelligent machine is the _last_ invention that man need ever make, provided that the machine is docile enough to tell us how to keep it under control. ... It is more probable than not that, within the twentieth century, an ultraintelligent machine will be built and that it will be the last invention that man need make.

Good has captured the essence of the runaway, but does not pursue its most disturbing consequences. Any intelligent machine of the sort he describes would not be humankind's "tool" -- any more than humans are the tools of rabbits or robins or chimpanzees.

Through the '60s and '70s and '80s, recognition of the cataclysm spread [29] [1] [31] [5].

Perhaps it was the science-fiction writers who felt the first concrete impact. After all, the "hard" science-fiction writers are the ones who try to write specific stories about all that technology may do for us.

More and more, these writers felt an opaque wall across the future. Once, they could put such fantasies millions of years in the future [24]. Now they saw that their most diligent extrapolations resulted in the unknowable ... soon. Once, galactic empires might have seemed a Post-Human domain. Now, sadly, even interplanetary ones are.

What about the '90s and the '00s and the '10s, as we slide toward the edge? How will the approach of the Singularity spread across the human world view? For a while yet, the general critics of machine sapience will have good press.

After all, till we have hardware as powerful as a human brain it is probably foolish to think we'll be able to create human equivalent (or greater) intelligence. (There is the far-fetched possibility that we could make a human equivalent out of less powerful hardware, if we were willing to give up speed, if we were willing to settle for an artificial being who was literally slow [30].

But it's much more likely that devising the software will be a tricky process, involving lots of false starts and experimentation. If so, then the arrival of self-aware machines will not happen till after the development of hardware that is substantially more powerful than humans' natural equipment.)

But as time passes, we should see more symptoms. The dilemma felt by science fiction writers will be perceived in other creative endeavors. (I have heard thoughtful comic book writers worry about how to have spectacular effects when everything visible can be produced by the technologically commonplace.)

We will see automation replacing higher and higher level jobs. We have tools right now (symbolic math programs, cad/cam) that release us from most low-level drudgery.

Or put another way: The work that is truly productive is the domain of a steadily smaller and more elite fraction of humanity. In the coming of the Singularity, we are seeing the predictions of _true_ technological unemployment finally come true.

Another symptom of progress toward the Singularity: ideas themselves should spread ever faster, and even the most radical will quickly become commonplace.

When I began writing science fiction in the middle '60s, it seemed very easy to find ideas that took decades to percolate into the cultural consciousness; now the lead time seems more like eighteen months. (Of course, this could just be me losing my imagination as I get old, but I see the effect in others too.)

Like the shock in a compressible flow, the Singularity moves closer as we accelerate through the critical speed.

And what of the arrival of the Singularity itself? What can be said of its actual appearance? Since it involves an intellectual runaway, it will probably occur faster than any technical revolution seen so far.

The precipitating event will likely be unexpected -- perhaps even to the researchers involved. ("But all our previous models were catatonic!

We were just tweaking some parameters....") If networking is widespread enough (into ubiquitous embedded systems), it may seem as if our artifacts as a whole had suddenly wakened.

And what happens a month or two (or a day or two) after that? I have only analogies to point to: The rise of humankind. We will be in the Post-Human era. And for all my rampant technological optimism, sometimes I think I'd be more comfortable if I were regarding these transcendental events from one thousand years remove ... instead of twenty.

Can the Singularity be Avoided?

Well, maybe it won't happen at all: Sometimes I try to imagine the symptoms that we should expect to see if the Singularity is not to develop.

There are the widely respected arguments of Penrose [19] and Searle [22] against the practicality of machine sapience. In August of 1992, Thinking Machines Corporation held a workshop to investigate the question "How We Will Build a Machine that Thinks" [27].

As you might guess from the workshop's title, the participants were not especially supportive of the arguments against machine intelligence.

In fact, there was general agreement that minds can exist on nonbiological substrates and that algorithms are of central importance to the existence of minds.

However, there was much debate about the raw hardware power that is present in organic brains. A minority felt that the largest 1992 computers were within three orders of magnitude of the power of the human brain.

The majority of the participants agreed with Moravec's estimate [17] that we are ten to forty years away from hardware parity.

And yet there was another minority who pointed to [7] [21], and conjectured that the computational competence of single neurons may be far higher than generally believed.

If so, our present computer hardware might be as much as _ten_ orders of magnitude short of the equipment we carry around in our heads. If this is true (or for that matter, if the Penrose or Searle critique is valid), we might never see a Singularity.

Instead, in the early '00s we would find our hardware performance curves beginning to level off -- this because of our inability to automate the design work needed to support further hardware improvements.

We'd end up with some _very_ powerful hardware, but without the ability to push it further.

Commercial digital signal processing might be awesome, giving an analog appearance even to digital operations, but nothing would ever "wake up" and there would never be the intellectual runaway which is the essence of the Singularity.

It would likely be seen as a golden age ... and it would also be an end of progress. This is very like the future predicted by Gunther Stent. In fact, on page 137 of [25], Stent explicitly cites the development of transhuman intelligence as a sufficient condition to break his projections.

But if the technological Singularity can happen, it will. Even if all the governments of the world were to understand the "threat" and be in deadly fear of it, progress toward the goal would continue. In fiction, there have been stories of laws passed forbidding the construction of "a machine in the likeness of the human mind" [13].

In fact, the competitive advantage -- economic, military, even artistic -- of every advance in automation is so compelling that passing laws, or having customs, that forbid such things merely assures that someone else will get them first.

Eric Drexler [8] has provided spectacular insights about how far technical improvement may go. He agrees that superhuman intelligences will be available in the near future -- and that such entities pose a threat to the human status quo.

But Drexler argues that we can confine such transhuman devices so that their results can be examined and used safely.

This is I. J. Good's ultraintelligent machine, with a dose of caution.

I argue that confinement is intrinsically impractical. For the case of physical confinement: Imagine yourself locked in your home with only limited data access to the outside, to your masters.

If those masters thought at a rate -- say -- one million times slower than you, there is little doubt that over a period of years (your time) you could come up with "helpful advice" that would incidentally set you free. (I call this "fast thinking" form of superintelligence "weak superhumanity".

Such a "weakly superhuman" entity would probably burn out in a few weeks of outside time.

"Strong superhumanity" would be more than cranking up the clock speed on a human-equivalent mind.

It's hard to say precisely what "strong superhumanity" would be like, but the difference appears to be profound. Imagine running a dog mind at very high speed.

Would a thousand years of doggy living add up to any human insight? (Now if the dog mind were cleverly rewired and _then_ run at high speed, we might see something different....) Many speculations about superintelligence seem to be based on the weakly superhuman model.

I believe that our best guesses about the post-Singularity world can be obtained by thinking on the nature of strong superhumanity. I will return to this point later in the paper.)

Another approach to confinement is to build _rules_ into the mind of the created superhuman entity (for example, Asimov's Laws [3]).

I think that any rules strict enough to be effective would also produce a device whose ability was clearly inferior to the unfettered versions (and so human competition would favor the development of the those more dangerous models).

Still, the Asimov dream is a wonderful one: Imagine a willing slave, who has 1000 times your capabilities in every way.

Imagine a creature who could satisfy your every safe wish (whatever that means) and still have 99.9% of its time free for other activities.

There would be a new universe we never really understood, but filled with benevolent gods (though one of _my_ wishes might be to become one of them).

If the Singularity can not be prevented or confined, just how bad could the Post-Human era be? Well ... pretty bad. The physical extinction of the human race is one possibility. (Or as Eric Drexler put it of nanotechnology: Given all that such technology can do, perhaps governments would simply decide that they no longer need citizens!).

Yet physical extinction may not be the scariest possibility. Again, analogies: Think of the different ways we relate to animals. Some of the crude physical abuses are implausible, yet.... In a Post-Human world there would still be plenty of niches where human equivalent automation would be desirable: embedded systems in autonomous devices, self-aware daemons in the lower functioning of larger sentients. (A strongly superhuman intelligence would likely be a Society of Mind [16] with some very competent components.) Some of these human equivalents might be used for nothing more than digital signal processing.

They would be more like whales than humans. Others might be very human-like, yet with a one-sidedness, a _dedication_ that would put them in a mental hospital in our era.

Though none of these creatures might be flesh-and-blood humans, they might be the closest things in the new enviroment to what we call human now. (I. J. Good had something to say about this, though at this late date the advice may be moot: Good [12] proposed a "Meta-Golden Rule", which might be paraphrased as "Treat your inferiors as you would be treated by your superiors."

It's a wonderful, paradoxical idea (and most of my friends don't believe it) since the game-theoretic payoff is so hard to articulate. Yet if we were able to follow it, in some se

I have argued above that we cannot prevent the Singularity, that its coming is an inevitable consequence of the humans' natural competitiveness and the possibilities inherent in technology. And yet ... we are the initiators.

Even the largest avalanche is triggered by small things. We have the freedom to establish initial conditions, make things happen in ways that are less inimical than others.

Of course (as with starting avalanches), it may not be clear what the right guiding nudge really is:

Other Paths to the Singularity: Intelligence Amplification_

When people speak of creating superhumanly intelligent beings, they are usually imagining an AI project.

But as I noted at the beginning of this paper, there are other paths to superhumanity. Computer networks and human-computer interfaces seem more mundane than AI, and yet they could lead to the Singularity.

I call this contrasting approach Intelligence Amplification (IA). IA is something that is proceeding very naturally, in most cases not even recognized by its developers for what it is.

But every time our ability to access information and to communicate it to others is improved, in some sense we have achieved an increase over natural intelligence. Even now, the team of a PhD human and good computer workstation (even an off-net workstation!) could probably max any written intelligence test in existence.

And it's very likely that IA is a much easier road to the achievement of superhumanity than pure AI. In humans, the hardest development problems have already been solved.

Building up from within ourselves ought to be easier than figuring out first what we really are and then building machines that are all of that. And there is at least conjectural precedent for this approach. Cairns-Smith [6] has speculated that biological life may have begun as an adjunct to still more primitive life based on crystalline growth.

Lynn Margulis (in [15] and elsewhere) has made strong arguments that mutualism is a great driving force in evolution.

Note that I am not proposing that AI research be ignored or less funded. What goes on with AI will often have applications in IA, and vice versa.

I am suggesting that we recognize that in network and interface research there is something as profound (and potential wild) as Artificial Intelligence.

With that insight, we may see projects that are not as directly applicable as conventional interface and network design work, but which serve to advance us toward the Singularity along the IA path.

Here are some possible projects that take on special significance, given the IA point of view:

Human/computer team automation: Take problems that are normally considered for purely machine solution (like hill-climbing problems), and design programs and interfaces that take a advantage of humans' intuition and available computer hardware.

Considering all the bizarreness of higher dimensional hill-climbing problems (and the neat algorithms that have been devised for their solution), there could be some very interesting displays and control tools provided to the human team member.

Develop human/computer symbiosis in art: Combine the graphic generation capability of modern machines and the esthetic sensibility of humans.

Of course, there has been an enormous amount of research in designing computer aids for artists, as labor saving tools. I'm suggesting that we explicitly aim for a greater merging of competence, that we explicitly recognize the cooperative approach that is possible. Karl Sims [23] has done wonderful work in this direction.

Allow human/computer teams at chess tournaments. We already have programs that can play better than almost all humans. But how much work has been done on how this power could be used by a human, to get something even better?

If such teams were allowed in at least some chess tournaments, it could have the positive effect on IA research that allowing computers in tournaments had for the corresponding niche in AI.

Develop interfaces that allow computer and network access without requiring the human to be tied to one spot, sitting in front of a computer. (This is an aspect of IA that fits so well with known economic advantages that lots of effort is already being spent on it.)

Develop more symmetrical decision support systems. A popular research/product area in recent years has been decision support systems. This is a form of IA, but may be too focussed on systems that are oracular.

As much as the program giving the user information, there must be the idea of the user giving the program guidance.

Use local area nets to make human teams that really work (ie, are more effective than their component members). This is generally the area of "groupware", already a very popular commercial pursuit.

The change in viewpoint here would be to regard the group activity as a combination organism. In one sense, this suggestion might be regarded as the goal of inventing a "Rules of Order" for such combination operations.

For instance, group focus might be more easily maintained than in classical meetings. Expertise of individual human members could be isolated from ego issues such that the contribution of different members is focussed on the team project.

And of course shared data bases could be used much more conveniently than in conventional committee operations. (Note that this suggestion is aimed at team operations rather than political meetings.

In a political setting, the automation described above would simply enforce the power of the persons making the rules!)

Exploit the worldwide Internet as a combination human/machine tool.

Of all the items on the list, progress in this is proceeding the fastest and may run us into the Singularity before anything else.

The power and influence of even the present-day Internet is vastly underestimated.

For instance, I think our contemporary computer systems would break under the weight of their own complexity if it weren't for the edge that the USENET "group mind" gives the system administration and support people!

The very anarchy of the worldwide net development is evidence of its potential. As connectivity and bandwidth and archive size and computer speed all increase, we are seeing something like Lynn Margulis' [15] vision of the biosphere as data processor recapitulated, but at a million times greater speed and with millions of humanly intelligent agents (ourselves).

The above examples illustrate research that can be done within the context of contemporary computer science departments. There are other paradigms.

For example, much of the work in Artificial Intelligence and neural nets would benefit from a closer connection with biological life. Instead of simply trying to model and understand biological life with computers, research could be directed toward the creation of composite systems that rely on biological life for guidance or for the providing features we don't understand well enough yet to implement in hardware.

A long-time dream of science-fiction has been direct brain to computer interfaces [2] [29]. In fact, there is concrete work that can be done (and is being done) in this area:

Limb prosthetics is a topic of direct commercial applicability. Nerve to silicon transducers can be made [14].

This is an exciting, near-term step toward direct communication.

Direct links into brains seem feasible, if the bit rate is low: given human learning flexibility, the actual brain neuron targets might not have to be precisely selected.

Even 100 bits per second would be of great use to stroke victims who would otherwise be confined to menu-driven interfaces.

Plugging in to the optic trunk has the potential for bandwidths of 1 Mbit/second or so. But for this, we need to know the fine-scale architecture of vision, and we need to place an enormous web of electrodes with exquisite precision.

If we want our high bandwidth connection to be _in addition_ to what paths are already present in the brain, the problem becomes vastly more intractable. Just sticking a grid of high-bandwidth receivers into a brain certainly won't do it.

But suppose that the high-bandwidth grid were present while the brain structure was actually setting up, as the embryo develops.

That suggests: Animal embryo experiments. I wouldn't expect any IA success in the first years of such research, but giving developing brains access to complex simulated neural structures might be very interesting to the people who study how the embryonic brain develops.

In the long run, such experiments might produce animals with additional sense paths and interesting intellectual abilities.

Originally, I had hoped that this discussion of IA would yield some clearly safer approaches to the Singularity. (After all, IA allows our participation in a kind of transcendance.)

Alas, looking back over these IA proposals, about all I am sure of is that they should be considered, that they may give us more options. But as for safety ... well, some of the suggestions are a little scarey on their face.

One of my informal reviewers pointed out that IA for individual humans creates a rather sinister elite. We humans have millions of years of evolutionary baggage that makes us regard competition in a deadly light.

Much of that deadliness may not be necessary in today's world, one where losers take on the winners' tricks and are coopted into the winners' enterprises.

A creature that was built _de novo_ might possibly be a much more benign entity than one with a kernel based on fang and talon. And even the egalitarian view of an Internet that wakes up along with all mankind can be viewed as a nightmare [26].

The problem is not simply that the Singularity represents the passing of humankind from center stage, but that it contradicts our most deeply held notions of being. I think a closer look at the notion of strong superhumanity can show why that is.

Strong Superhumanity and the Best We Can Ask for

Suppose we could tailor the Singularity. Suppose we could attain our most extravagant hopes. What then would we ask for: That humans themselves would become their own successors, that whatever injustice occurs would be tempered by our knowledge of our roots.

For those who remained unaltered, the goal would be benign treatment (perhaps even giving the stay-behinds the appearance of being masters of godlike slaves).

It could be a golden age that also involved progress (overleaping Stent's barrier). Immortality (or at least a lifetime as long as we can make the universe survive [10] [4]) would be achievable.

But in this brightest and kindest world, the philosophical problems themselves become intimidating.

A mind that stays at the same capacity cannot live forever; after a few thousand years it would look more like a repeating tape loop than a person. (The most chilling picture I have seen of this is in [18].)

To live indefinitely long, the mind itself must grow ... and when it becomes great enough, and looks back ... what fellow-feeling can it have with the soul that it was originally?

Certainly the later being would be everything the original was, but so much vastly more. And so even for the individual, the Cairns-Smith or Lynn Margulis notion of new life growing incrementally out of the old must still be valid.

This "problem" about immortality comes up in much more direct ways. The notion of ego and self-awareness has been the bedrock of the hardheaded rationalism of the last few centuries.

Yet now the notion of self-awareness is under attack from the Artificial Intelligence people ("self-awareness and other delusions").

Intelligence Amplification undercuts our concept of ego from another direction.

The post-Singularity world will involve extremely high-bandwidth networking. A central feature of strongly superhuman entities will likely be their ability to communicate at variable bandwidths, including ones far higher than speech or written messages.

What happens when pieces of ego can be copied and merged, when the size of a selfawareness can grow or shrink to fit the nature of the problems under consideration?

These are essential features of strong superhumanity and the Singularity. Thinking about them, one begins to feel how essentially strange and different the Post-Human era will be -- _no matter how cleverly and benignly it is brought to be_.

From one angle, the vision fits many of our happiest dreams: a time unending, where we can truly know one another and understand the deepest mysteries. From another angle, it's a lot like the worst- case scenario I imagined earlier in this paper.

Which is the valid viewpoint? In fact, I think the new era is simply too different to fit into the classical frame of good and evil.

That frame is based on the idea of isolated, immutable minds connected by tenuous, low-bandwith links. But the post-Singularity world _does_ fit with the larger tradition of change and cooperation that started long ago (perhaps even before the rise of biological life). I think there _are_ notions of ethics that would apply in such an era.

Research into IA and high-bandwidth communications should improve this understanding.

I see just the glimmerings of this now [32]. There is Good's Meta-Golden Rule; perhaps there are rules for distinguishing self from others on the basis of bandwidth of connection.

And while mind and self will be vastly more labile than in the past, much of what we value (knowledge, memory, thought) need never be lost.

I think Freeman Dyson has it right when he says [9]: "God is what mind becomes when it has passed beyond the scale of our comprehension."

[I wish to thank John Carroll of San Diego State University and Howard Davidson of Sun Microsystems for discussing the draft version of this paper with me.]

Annotated Sources [and an occasional plea for bibliographical help]

[1] Alfve'n, Hannes, writing as Olof Johanneson, _The End of Man?_, Award Books, 1969 earlier published as "The Tale of the Big Computer", Coward-McCann, translated from a book copyright 1966 Albert Bonniers Forlag AB with English translation copyright 1966 by Victor Gollanz, Ltd.

[2] Anderson, Poul, "Kings Who Die", _If_, March 1962, p8-36. Reprinted in _Seven Conquests_, Poul Anderson, MacMillan Co., 1969.

[3] Asimov, Isaac, "Runaround", _Astounding Science Fiction_, March 1942, p94. Reprinted in _Robot Visions_, Isaac Asimov, ROC, 1990. Asimov describes the development of his robotics stories in this book.

[4] Barrow, John D. and Frank J. Tipler, _The Anthropic Cosmological Principle_, Oxford University Press, 1986.

[5] Bear, Greg, "Blood Music", _Analog Science Fiction-Science Fact_, June, 1983. Expanded into the novel _Blood Music_, Morrow, 1985.

[6] Cairns-Smith, A. G., _Seven Clues to the Origin of Life_, Cambridge University Press, 1985.

[7] Conrad, Michael _et al._, "Towards an Artificial Brain", _BioSystems_, vol 23, pp175-218, 1989.

[8] Drexler, K. Eric, _Engines of Creation_, Anchor Press/Doubleday, 1986.

[9] Dyson, Freeman, _Infinite in All Directions_, Harper && Row, 1988.

[10] Dyson, Freeman, "Physics and Biology in an Open Universe", _Review of Modern Physics_, vol 51, pp447-460, 1979.

[11] Good, I. J., "Speculations Concerning the First Ultraintelligent Machine", in _Advances in Computers_, vol 6, Franz L. Alt and Morris Rubinoff, eds, pp31-88, 1965, Academic Press.

[12] Good, I. J., [Help! I can't find the source of Good's Meta-Golden Rule, though I have the clear recollection of hearing about it sometime in the 1960s. Through the help of the net, I have found pointers to a number of related items. G. Harry Stine and Andrew Haley have written about metalaw as it might relate to extraterrestrials: G. Harry Stine, "How to Get along with Extraterrestrials ... or Your Neighbor", _Analog Science Fact- Science Fiction_, February, 1980, p39-47.] [13] Herbert, Frank, _Dune_, Berkley Books, 1985. However, this novel was serialized in _Analog Science Fiction-Science Fact_ in the 1960s.

[14] Kovacs, G. T. A. _et al._, "Regeneration Microelectrode Array for Peripheral Nerve Recording and Stimulation", _IEEE Transactions on Biomedical Engineering_, v 39, n 9, pp 893-902.

[15] Margulis, Lynn and Dorion Sagan, _Microcosmos, Four Billion Years of Evolution from Our Microbial Ancestors_, Summit Books, 1986.

[16] Minsky, Marvin, _Society of Mind_, Simon and Schuster, 1985.

[17] Moravec, Hans, _Mind Children_, Harvard University Press, 1988.

[18] Niven, Larry, "The Ethics of Madness", _If_, April 1967, pp82-108. Reprinted in _Neutron Star_, Larry Niven, Ballantine Books, 1968.

[19] Penrose, Roger, _The Emperor's New Mind_, Oxford University Press, 1989.

[20] Platt, Charles, Private Communication.

[21] Rasmussen, S. _et al._, "Computational Connectionism within Neurons: a Model of Cytoskeletal Automata Subserving Neural Networks", in _Emergent Computation_, Stephanie Forrest, ed., pp428-449, MIT Press, 1991.

[22] Searle, John R., "Minds, Brains, and Programs", in _The Behavioral and Brain Sciences_, vol 3, Cambridge University Press, 1980. The essay is reprinted in _The Mind's I_, edited by Douglas R. Hofstadter and Daniel C. Dennett, Basic Books, 1981 (my source for this reference). This reprinting contains an excellent critique of the Searle essay.

[23] Sims, Karl, "Interactive Evolution of Dynamical Systems", Thinking Machines Corporation, Technical Report Series (published in _Toward a Practice of Autonomous Systems: Proceedings of the First European Conference on Artificial Life_, Paris, MIT Press, December 1991.

[24] Stapledon, Olaf, _The Starmaker_, Berkley Books, 1961 (but from the date on forward, probably written before 1937).

[25] Stent, Gunther S., _The Coming of the Golden Age: A View of the End of Progress_, The Natural History Press, 1969.

[26] Swanwick Michael, _Vacuum Flowers_, serialized in _Isaac Asimov's Science Fiction Magazine_, December(?) 1986 - February 1987. Republished by Ace Books, 1988.

[27] Thearling, Kurt, "How We Will Build a Machine that Thinks", a workshop at Thinking Machines Corporation, August 24-26, 1992. Personal Communication.

[28] Ulam, S., Tribute to John von Neumann, _Bulletin of the American Mathematical Society_, vol 64, nr 3, part 2, May 1958, pp1-49.

[29] Vinge, Vernor, "Bookworm, Run!", _Analog_, March 1966, pp8-40. Reprinted in _True Names and Other Dangers_, Vernor Vinge, Baen Books, 1987.

[30] Vinge, Vernor, "True Names", _Binary Star Number 5_, Dell, 1981. Reprinted in _True Names and Other Dangers_, Vernor Vinge, Baen Books, 1987.

[31] Vinge, Vernor, First Word, _Omni_, January 1983, p10.

[32] Vinge, Vernor, To Appear [ :-) ].

QUANTA

Friday, October 4, 2013

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Cells from small biopsies can be used to grow large numbers of a patient’s own protective brain cells

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MIT inventor unleashes hundreds of self-assembling cube swarmbots

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Thursday, October 3, 2013

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The secret of longevity for the world’s longest-living rodent: better protein creation

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Seeing cells through silicon microfluidic devices

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Is ‘massive open online research’ (MOOR) the next frontier for education?

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Wednesday, October 2, 2013

New programming language directs DNA to build custom-designed molecules

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Why glial cells should be included in the BRAIN initative

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Why don’t we have fusion yet?

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Extending MRI to nanoscale resolution

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Tuesday, October 1, 2013

How to make ceramics that bend without breaking

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NASA space telescopes find patchy clouds on exotic world

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NASA wants investigations for a Mars 2020 rover

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A hidden genetic code for better designer genes

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Human on a chip

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Monday, September 30, 2013

Syria's War Viewed Almost in Real Time

For the first time, the war in Syria has given global audiences a close-up view of war