Potential 'Game Changer' for Pathologists

Balis isn't playing war games. The director of the Division of Pathology Informatics at the University of Michigan Medical School is demonstrating the extreme flexibility of a software-tool aimed at making the detection of abnormalities in cell and tissue samples faster, more accurate and more consistent.

In a medical setting, instead of helicopters, the technique, known as Spatially-Invariant Vector Quantization (SIVQ), can pinpoint cancer cells and other critical features from digital images made from tissue slides.

But SIVQ isn't limited to any particular area of medicine. It can readily separate calcifications from malignancies in breast tissue samples, search for and count particular cell types in a bone marrow slide, or quickly identify the cherry red nucleoli of cells associated with Hodgkin's disease, according to findings just published in theJournal of Pathology Informatics.

"The fact that the algorithm operates effortlessly across domains and lengths scales, while requiring minimal user training, sets it apart from conventional approaches to image analysis," Balis says.

The technology -- developed in conjunction with researchers at Massachusetts General Hospital and Harvard Medical School -- differs from conventional pattern recognition software by basing its core search on a series of concentric, pattern-matching rings, rather than the more typical rectangular or square blocks. This approach takes advantage of the rings' continuous symmetry, allowing for the recognition of features no matter how they're rotated or whether they're reversed, like in a mirror.

"That's good because in pathology, images of cells and tissue do not have a particular orientation," Balis says."They can face any direction." One of the images included with the paper demonstrates this principle; SIVQ consistently identifies the letter A from a field of text, no matter how the letters are rotated.

How it works

In SIVQ, a search starts with the user selecting a small area of pixels, known as a vector, which she wants to try to match elsewhere in the image. The vector can also come from a stored library of images.

The algorithm then compares this circular vector to every part of the image. And at every location, the ring rotates through millions of possibilities in an attempt to find a match in every possible degree of rotation. Smaller rings within the main ring can provide an even more refined search.

The program then creates a heat map, shading the image based on the quality of match at every point.

This technique wouldn't work with a square or rectangular-shaped search structure because those shapes don't remain symmetrical as they rotate, Balis explains.

Why hasn't everyone been using circles all along?

"It's one of those things that's only obvious in hindsight," Balis says.

In testing the algorithm, researchers even used it to find Waldo in an illustration from a Where's Waldo? children's book.

"You just have to generate a vector for his face," explains Jason Hipp, M.D., Ph.D., co-lead author of the paper -- just as one would generate a vector to recognize calcifications in breast tissue.

A"game changer"

Hipp believes the technology has the potential to be a"game changer" for the field by opening myriad new possibilities for deeper image analysis.

"It's going to allow us to think about things differently," says Hipp, a pathology informatics research fellow and clinical lecturer in the Department of Pathology."We're starting to bridge the gap between the qualitative analysis carried out by trained expert pathologists with the quantitative approaches made possible by advances in imaging technology."

For example, the most common way to look at tissue samples is still a staining technique that dates back to the1800s. Reading these complex slides and rendering a diagnosis is part of the art of pathology.

SIVQ, however, can assist pathologists by pre-screening an image and identifying potentially problematic areas, including subtle features that may not be readily apparent to the eye.

SIVQ's efficiency in pre-identifying potential problems becomes apparent when one considers that a pathologist may review more than 100 slides in a single day.

"Unlike even the most diligent humans, computers do not suffer from the effects of boredom or fatigue," Balis says.

Working together

Vectors can also be pooled to create shared libraries -- a catalog of reference images upon which the computer can search -- Balis explains, which could help pathologists to quickly identify rare anomalies.

"Bringing such tools into the clinical workflow could provide a higher level of expertise that is distributed more widely, and lower the rate at which findings get overlooked," Balis says.

Following the publication of this first paper presenting the SIVQ algorithm, the team has a number of research projects nearing completion that demonstrate the technology's potential usefulness in a number of basic science and clinical applications. These efforts involve collaborations with researchers at the National Institutes of Health, Mayo Clinic, Rutgers University, Harvard Medical School and Massachusetts General Hospital.

SIVQ may also help with the analysis of"liquid biopsies," an experimental technique of scanning blood samples for tiny numbers of cancer cells hiding amid billions of healthy ones. Balis was involved with the development of that technology at Massachusetts General Hospital before he came to U-M and members of that research team are also involved in developing SIVQ and its applications.

Still, pathologists shouldn't be worried that SIVQ will put them out of a job.

"No one is talking about replacing pathologists any time soon," Balis says."But working in tandem with this technology, the hope is that they will be able to achieve a higher overall level of performance."

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Atomic Antennas Transmit Quantum Information Across a Microchip

The researchers have published their work in the scientific journalNature.

Six years ago scientists at the University of Innsbruck realized the first quantum byte -- a quantum computer with eight entangled quantum particles; a record that still stands."Nevertheless, to make practical use of a quantum computer that performs calculations, we need a lot more quantum bits," says Prof. Rainer Blatt, who, with his research team at the Institute for Experimental Physics, created the first quantum byte in an electromagnetic ion trap."In these traps we cannot string together large numbers of ions and control them simultaneously."

To solve this problem, the scientists have started to design a quantum computer based on a system of many small registers, which have to be linked. To achieve this, Innsbruck quantum physicists have now developed a revolutionary approach based on a concept formulated by theoretical physicists Ignacio Cirac and Peter Zoller. In their experiment, the physicists electromagnetically coupled two groups of ions over a distance of about 50 micrometers. Here, the motion of the particles serves as an antenna."The particles oscillate like electrons in the poles of a TV antenna and thereby generate an electromagnetic field," explains Blatt."If one antenna is tuned to the other one, the receiving end picks up the signal of the sender, which results in coupling." The energy exchange taking place in this process could be the basis for fundamental computing operations of a quantum computer.

Antennas amplify transmission

"We implemented this new concept in a very simple way," explains Rainer Blatt. In a miniaturized ion trap a double-well potential was created, trapping the calcium ions. The two wells were separated by 54 micrometers."By applying a voltage to the electrodes of the ion trap, we were able to match the oscillation frequencies of the ions," says Blatt.

"This resulted in a coupling process and an energy exchange, which can be used to transmit quantum information." A direct coupling of two mechanical oscillations at the quantum level has never been demonstrated before. In addition, the scientists show that the coupling is amplified by using more ions in each well."These additional ions function as antennas and increase the distance and speed of the transmission," says Rainer Blatt, who is excited about the new concept. This work constitutes a promising approach for building a fully functioning quantum computer.

"The new technology offers the possibility to distribute entanglement. At the same time, we are able to target each memory cell individually," explains Rainer Blatt. The new quantum computer could be based on a chip with many micro traps, where ions communicate with each other through electromagnetic coupling. This new approach represents an important step towards practical quantum technologies for information processing.

The quantum researchers are supported by the Austrian Science Fund FWF, the European Union, the European Research Council and the Federation of Austrian Industries Tyrol.

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Etched Quantum Dots Shape Up as Single Photon Emitters

The conventional way to build quantum dots -- at NIST and elsewhere -- is to grow them like crystals in a solution, but this somewhat haphazard process results in irregular shapes. The new, more precise process was developed by NIST postdoctoral researcher Varun Verma when he was a student at the University of Illinois. Verma uses electron beam lithography and etching to carve quantum dots inside a semiconductor sandwich (called a quantum well) that confines particles in two dimensions. Lithography controls the dot's size and position, while sandwich thickness and composition -- as well as dot size -- can be used to tune the color of the dot's light emissions.

Some quantum dots are capable of emitting individual, isolated photons on demand, a crucial trait for quantum information systems that encode information by manipulating single photons. In new work reported inOptics Express, NIST tests demonstrated that the lithographed and etched quantum dots do indeed work as sources of single photons. The tests were performed on dots made of indium gallium arsenide. Dots of various diameters were patterned in specific positions in square arrays. Using a laser to excite individual dots and a photon detector to analyze emissions, NIST researchers found that dots 35 nanometers (nm) wide, for instance, emitted nearly all light at a wavelength of 888.6 nm. The timing pattern indicated that the light was emitted as a train of single photons.

NIST researchers now plan to construct reflective cavities around individual etched dots to guide their light emissions. If each dot can emit most photons perpendicular to the chip surface, more light can be collected to make a more efficient single photon source. Vertical emission has been demonstrated with crystal-grown quantum dots, but these dots can't be positioned or distributed reliably in cavities. Etched dots offer not only precise positioning but also the possibility of making identical dots, which could be used to generate special states of light such as two or more photons that are entangled, a quantum phenomenon that links their properties even at a distance.

The quantum dots tested in the experiments were made at NIST. A final step was carried out at the University of Illinois, where a crystal layer was grown over the dots to form clean interfaces.

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A Semantic Sommelier: Wine Application Highlights the Power of Web 3.0

Web scientist and Rensselaer Polytechnic Institute Tetherless World Research Constellation Professor Deborah McGuinness has been developing a family of applications for the most tech-savvy wine connoisseurs since her days as a graduate student in the 1980s -- before what we now know as the World Wide Web had even been envisioned.

Today, McGuinness is among the world's foremost experts in Web ontology languages. These languages are used to encode meanings in a language that computers can understand. The most recent version of her wine application serves as an exceptional example of what the future of the World Wide Web, often called Web 3.0, might in fact look like. It is also an exceptional tool for teaching future Web Scientists about ontologies.

"The wine agent came about because I had to demonstrate the new technology that I was developing," McGuinness said."I had sophisticated applications that used cutting-edge artificial intelligence technology in domains, such as telecommunications equipment, that were difficult for anyone other than well-trained engineers to understand." McGuinness took the technology into the domain of wines and foods to create a program that she uses as a semantic tutorial, an"Ontologies 101" as she calls it. And students throughout the years have done many things with the wine agent including, most recently, experimentation with social media and mobile phone applications.

Today, the semantic sommelier is set to provide even the most novice of foodies some exciting new tools to expand their wine knowledge and food-pairing abilities on everything from their home PC to their smart phone. Evan Patton, a graduate student in computer science at Rensselaer, is the most recent student to tinker with the wine agent and is working with McGuinness to bring it into the mobile space on both the iPhone and Droid platforms.

The agent uses the Web Ontology Language (OWL), the formal language for the Semantic Web. Like the English language, which uses an agreed upon alphabet to form words and sentences that all English-speaking people can recognize, OWL uses a formalized set of symbols to create a code or language that a wide variety of applications can"read." This allows your computer to operate more efficiently and more intelligently with your cell phone or your Facebook page, or any other webpage or web-enabled device. These semantics also allow for an entirely new generation in smart search technologies.

Thanks to its semantic technology, the sommelier is input with basic background knowledge about wine and food. For wine, that includes its body, color (red versus white or blush), sweetness, and flavor. For food, this includes the course (e.g. appetizer versus entrée), ingredient type (e.g. fish versus meat), and its heat (mild versus spicy). The semantic technologies beneath the application then encode that knowledge and apply reasoning to search and share that information. This semantic functionality can now be exploited for a variety of culinary purposes, all of which McGuinness, a personal lover of fine wines, and Patton are working together on.

Having a spicy fish dish for dinner? Search within the system and it will arrive at a good wine pairing for the meal. Beyond basic pairings, the application has strong possibilities for use in individual restaurants, according to McGuinness, who envisions teaming up with restaurant owners to input their specific menus and wine lists. Thus, a diner could check menus and wine holdings before going out for dinner or they could enter a restaurant, pull out their smart phone, and instantly know what is in the wine cellar and goes best with that chef's clams casino. Beyond pairings, diners could rate different wines, providing fellow diners with personal reviews and the restaurateur with valuable information on what to stock up on next week. Is it a dry restaurant? The application could also be loaded up with the inventory within the liquor store down the street.

Beyond the table, the application can also be used to make personal wine suggestions and virtual wine cellars that you could share with your friends via Facebook or other social media platforms. It could also be used to manage a personal wine cellar, providing information on what is a peak flavor at the moment or what in your cellar would go best with your famous steak au poivre.

"Today we have 10 gadgets with us at any given time," McGuinness said."We live and breathe social media. With semantic technologies, we can offload more of the searching and reasoning required to locate and share information to the computer while still maintaining personal control over our information and how we use it. We also increase the ability of our technologies to interact with each other and decrease the need for as many gadgets or as many interactions with them since the applications do more work for us."

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Quantum Simulator Becomes Accessible to the World

The researchers have published their work in the scientific journalNature.

Many phenomena in our world are based on the nature of quantum physics: the structure of atoms and molecules, chemical reactions, material properties, magnetism and possibly also certain biological processes. Since the complexity of phenomena increases exponentially with more quantum particles involved, a detailed study of these complex systems reaches its limits quickly; and conventional computers fail when calculating these problems. To overcome these difficulties, physicists have been developing quantum simulators on various platforms, such as neutral atoms, ions or solid-state systems, which, similar to quantum computers, utilize the particular nature of quantum physics to control this complexity.

In another breakthrough in this field, a team of young scientists in the research groups of Rainer Blatt and Peter Zoller at the Institute for Experimental Physics and Theoretical Physics of the University of Innsbruck and the Institute of Quantum Optics and Quantum Information (IQOQI) of the Austrian Academy of Sciences have been the first to engineer a comprehensive toolbox for an open-system quantum computer, which will enable researchers to construct more sophisticated quantum simulators for investigating complex problems in quantum physics.

Using controlled dissipation

The physicists use a natural phenomenon In their experiments that they usually try to minimize as much as possible: environmental disturbances. Such disturbances usually cause information loss in quantum systems and destroy fragile quantum effects such as entanglement or interference. In physics this deleterious process is called dissipation. Innsbruck researchers, led by experimental physicists Julio Barreiro and Philipp Schindler as well as the theorist Markus Müller, have now been first in using dissipation in a quantum simulator with trapped ions in a beneficial way and engineered system-environment coupling experimentally.

"We not only control all internal states of the quantum system consisting of up to four ions but also the coupling to the environment," explains Julio Barreiro."In our experiment we use an additional ion that interacts with the quantum system and, at the same time, establishes a controlled contact to the environment," explains Philipp Schindler. The surprising result is that by using dissipation, the researchers are able to generate and intensify quantum effects, such as entanglement, in the system."We achieved this by controlling the disruptive environment," says an excited Markus Müller.

Putting the quantum world into order

In one of their experiments the researchers demonstrate the control of dissipative dynamics by entangling four ions using the environment ion."Contrary to other common procedures this also works irrespective of the initial state of each particle," explains Müller."Through a collective cooling process, the particles are driven to a common state." This procedure can be used to prepare many-body states, which otherwise could only be created and observed in an extremely well isolated quantum system.

The beneficial use of an environment allows for the realization of new types of quantum dynamics and the investigation of systems that have scarcely been accessible for experiments until now. In the last few years there has been continuous thinking about how dissipation, instead of suppressing it, could be actively used as a resource for building quantum computers and quantum memories. Innsbruck theoretical and experimental physicists cooperated closely and they have now been the first to successfully implement these dissipative effects in a quantum simulator.

The Innsbruck researchers are supported by the Austrian Science Fund (FWF), the European Commission and the Federation of Austrian Industries Tyrol.

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Quantum Hot Potato: Researchers Entice Two Atoms to Swap Smallest Energy Units

Described in a paper published Feb. 23 byNature, the NIST experiments enticed two beryllium ions (electrically charged atoms) to take turns vibrating in an electromagnetic trap, exchanging units of energy, or quanta, that are a hallmark of quantum mechanics. As little as one quantum was traded back and forth in these exchanges, signifying that the ions are"coupled" or linked together. These ions also behave like objects in the larger, everyday world in that they are"harmonic oscillators" similar to pendulums and tuning forks, making repetitive, back-and-forth motions.

"First one ion is jiggling a little and the other is not moving at all; then the jiggling motion switches to the other ion. The smallest amount of energy you could possibly see is moving between the ions," explains first author Kenton Brown, a NIST post-doctoral researcher."We can also tune the coupling, which affects how fast they exchange energy and to what degree. We can turn the interaction on and off."

The experiments were made possible by a novel, one-layer ion trap cooled to minus 269 C (minus 452 F) with a liquid helium bath. The ions, 40 micrometers apart, float above the surface of the trap. In contrast to a conventional two-layer trap, the surface trap features smaller electrodes and can position ions closer together, enabling stronger coupling. Chilling to cryogenic temperatures suppresses unwanted heat that can distort ion behavior.

The energy swapping demonstrations begin by cooling both ions with a laser to slow their motion. Then one ion is cooled further to a motionless state with two opposing ultraviolet laser beams. Next the coupling interaction is turned on by tuning the voltages of the trap electrodes. In separate experiments reported inNature, NIST researchers measured the ions swapping energy at levels of several quanta every 155 microseconds and at the single quantum level somewhat less frequently, every 218 microseconds. Theoretically, the ions could swap energy indefinitely until the process is disrupted by heating. NIST scientists observed two round-trip exchanges at the single quantum level.

To detect and measure the ions' activity, NIST scientists apply an oscillating pulse to the trap at different frequencies while illuminating both ions with an ultraviolet laser and analyzing the scattered light. Each ion has its own characteristic vibration frequency; when excited, the motion reduces the amount of laser light absorbed. Dimming of the scattered light tells scientists an ion is vibrating at a particular pulse frequency.

To turn on the coupling interaction, scientists use electrode voltages to tune the frequencies of the two ions, nudging them closer together. The coupling is strongest when the frequencies are closest. The motions become linked due to the electrostatic interactions of the positively charged ions, which tend to repel each other. Coupling associates each ion with both characteristic frequencies.

The new experiments are similar to the same NIST research group's 2009 demonstration of entanglement -- a quantum phenomenon linking properties of separated particles -- in a mechanical system of two separated pairs of vibrating ions. However, the new experiments coupled the oscillators' motions more directly than before and, therefore, may simplify information processing. In this case the researchers observed quantum behavior but did not verify entanglement.

The new technique could be useful in a future quantum computer, which would use quantum systems such as ions to solve problems that are intractable today. For example, quantum computers could break today's most widely used data encryption codes. Direct coupling of ions in separate locations could simplify logic operations and help correct processing errors. The technique is also a feature of proposals for quantum simulations, which may help explain the mechanisms of complex quantum systems such as high-temperature superconductors.

In addition, the demonstration also suggests that similar interactions could be used to connect different types of quantum systems, such as a trapped ion and a particle of light (photon), to transfer information in a future quantum network. For example, a trapped ion could act as a"quantum transformer" between a superconducting quantum bit (qubit) and a qubit made of photons.

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'Fingerprints' Match Molecular Simulations With Reality

ORNL's Jeremy Smith collaborated on devising a method -- dynamical fingerprints --that reconciles the different signals between experiments and computer simulations to strengthen analyses of molecules in motion. The research will be published in theProceedings of the National Academy of Sciences.

"Experiments tend to produce relatively simple and smooth-looking signals, as they only 'see' a molecule's motions at low resolution," said Smith, who directs ORNL's Center for Molecular Biophysics and holds a Governor's Chair at the University of Tennessee."In contrast, data from a supercomputer simulation are complex and difficult to analyze, as the atoms move around in the simulation in a multitude of jumps, wiggles and jiggles. How to reconcile these different views of the same phenomenon has been a long-standing problem."

The new method solves the problem by calculating peaks within the simulated and experimental data, creating distinct"dynamical fingerprints." The technique, conceived by Smith's former graduate student Frank Noe, now at the Free University of Berlin, can then link the two datasets.

Supercomputer simulations and modeling capabilities can add a layer of complexity missing from many types of molecular experiments.

"When we started the research, we had hoped to find a way to use computer simulation to tell us which molecular motions the experiment actually sees," Smith said."When we were finished we got much more -- a method that could also tell us which other experiments should be done to see all the other motions present in the simulation. This method should allow major facilities like the ORNL's Spallation Neutron Source to be used more efficiently."

Combining the power of simulations and experiments will help researchers tackle scientific challenges in areas like biofuels, drug development, materials design and fundamental biological processes, which require a thorough understanding of how molecules move and interact.

"Many important things in science depend on atoms and molecules moving," Smith said."We want to create movies of molecules in motion and check experimentally if these motions are actually happening."

"The aim is to seamlessly integrate supercomputing with the Spallation Neutron Source so as to make full use of the major facilities we have here at ORNL for bioenergy and materials science development," Smith said.

The collaborative work included researchers from L'Aquila, Italy, Wuerzburg and Bielefeld, Germany, and the University of California at Berkeley. The research was funded in part by a Scientific Discovery through Advanced Computing grant from the DOE Office of Science.

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