Defining Experience

Credit: Nick Reddyhoff

A better definition of consciousness will help with tough ethical choices.

• BY MORTEN OVERGAARD

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Much empirical research is devoted to the "hard problem," as the philosopher David Chalmers has put it, of why human information processing is accompanied by the subjective experience we call consciousness. Solving this problem has real clinical consequences for some patients (see "The Mystery Behind Anesthesia").

Researchers typically distinguish between the contents of consciousness and its levels. The contents of consciousness are our subjective experience, such as the taste of coffee. It is sometimes said that an experience ranks among the contents of consciousness if there is "something it is like" to have it. If there is something it is like, say, for a bat to have a sonar sense, then that sense is part of bats' consciousness.

Levels of consciousness, on the other hand, have to do with outward signs of a person's total or background state of awareness. Our understanding of these levels directly affects patient care. Today, we recognize three distinct "stages" of degraded consciousness based on a person's physical reactions. A person in a coma cannot be aroused and is considered unconscious. A person in a vegetative state is also unconscious but has signs of a normal sleep-wake cycle and may even appear to waken. Finally, a person is said to be in a minimally conscious state if an outside observer can see intermittent signs that he or she has some understanding of self or environment.

Yet these outer signs don't capture the core phenomenon of consciousness—subjective experience. To properly care for patients, we arguably need a new classification system more closely related to the contents of consciousness. Recent research is suggesting how we might create one. In one study, Adrian Owen and coworkers in the U.K. asked a patient in a vegetative state to think of certain mental images ("Imagine playing tennis" or "Imagine visiting the rooms in your house"). The resultant brain activation was no different from that observed in healthy control subjects, suggesting that some people in a vegetative state are more conscious than we realize. This technique was used to communicate with four out of 23 vegetative patients who would otherwise have been considered unconscious; they thought of tennis for "yes" and being in their house for "no."

Over the last few years, brain imaging studies like Owen's, along with other projects, have improved our tools for studying consciousness. While still indirect, such methods are still better than trying to assess consciousness by measuring something altogether different, like outward signs of contact with the world. A new classification system might help us predict which patients will benefit most from rehabilitation. It will certainly affect how we make the ethical decisions that arise when caring for patients with degraded consciousness.

Morten Overgaard studies the nature of consciousness as leader of the Cognitive Neuroscience Research Unit in Denmark.

Discovery Could Lead to an Exercise Pill

Technology Review

BIOMEDICINE

Discovery Could Lead to an Exercise Pill

A newly identified hormone acts like a workout, and transforms bad fat into good.

• WEDNESDAY, JANUARY 11, 2012
• BY KAREN WEINTRAUB

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Researchers have discovered a natural hormone that acts like exercise on muscle tissue—burning calories, improving insulin processing, and perhaps boosting strength. The scientists hope it could eventually be used as a treatment for obesity, diabetes, and, potentially, neuromuscular diseases like muscular dystrophy.

In a paper published online today by the journal Nature, the scientists, led by Bruce Spiegelman at the Dana-Farber Cancer Institute in Boston, showed that the hormone occurs naturally in both mice and humans. It pushes cells to transform from white fat—globules that serve as reservoirs for excess calories—into brown fat, which generates heat.

Because the hormone is present in both mice and humans, Spiegelman speculates that it may have served as an evolutionary defense against cold by triggering shivering. He named it irisin, after the Greek messenger goddess Iris, who allowed humans to communicate with the gods in Greek mythology, because exercise appears to "talk" to various tissues in the body via irisin.

Mice given irisin lost a few grams in the first 10 days after treatment, the study shows, and certain genes involved in powering the cell were turned on. Irisin also appeared to reduce the damage done by a high-fat diet, protecting mice against diet-induced obesity and diabetes, according to the paper, whose first author is postdoctoral fellow Pontus Boström.

"We are hopeful, though we have no evidence, that this hormone may embody some of the other benefits of exercise, perhaps in the neuromuscular system," Spiegelman says. If so, it could also be used to treat disorders like muscular dystrophy and muscle wasting.

Researchers still have to figure out how much benefit irisin could provide someone with diabetes or other health problems, says Spiegelman, also a professor of cell biology and medicine at Harvard Medical School. "I'm optimistic," he says. "I just don't want to overpromise and underdeliver."

Harvard Medical School's Dean Jeffrey Flier, an endocrinologist, says he is quite enthusiastic about the new hormone. The study, he says, "opens up a completely new approach to understanding the links between exercise, body weight, and diabetes."

Flier believes irisin offers strong therapeutic potential. "Though much remains to be learned about the action of irisin, and its status in humans with various diseases, this work has the potential to be a game-changer in the field of metabolic disease."

Last month, Spiegelman formed a Boston-based company named Ember Therapeutics to develop his brown-fat research projects, including irisin. The company raised $34 million in series A financing, and is backed by Third Rock Ventures of Boston.

Harvey Lodish, a professor of biology and bioengineering at MIT, and a member of the Whitehead Institute for Biomedical Research, says it may be harder to make irisin into a drug than Spiegelman anticipates. Lodish tried for years to make adiponectin, a hormone he discovered in the mid-1990s, into a similar drug, but never succeeded.

The concentration of both hormones in the blood is already so high that manufacturing enough to make a difference in health is quite challenging, he says. Maybe irisin will be easier to produce, he says, or maybe it could be delivered via gene therapy, in a modified version of the delivery system Spiegelman used in his research—but Lodish is dubious.

However, of Spiegelman's new research, he says, "It's very nice, it's very elegant." 

Research scientists link dietary DHA to male fertility

 by Biomechanism 

Who knew that male fertility depends on sperm-cell architecture? 

A University of Illinois study reports that a certain omega-3 fatty acid is necessary to construct the arch that turns a round, immature sperm cell into a pointy-headed super swimmer with an extra long tail.

“Normal sperm cells contain an arc-like structure called the acrosome that is critical in fertilization because it houses, organizes, and concentrates a variety of enzymes that sperm use to penetrate an egg,” said Manabu Nakamura, a U of I associate professor of biochemical and molecular nutrition.

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The study shows for the first time that docosahexaenoic acid (DHA) is essential in fusing the building blocks of the acrosome together. “Without DHA, this vital structure doesn’t form and sperm cells don’t work,” said Timothy Abbott, a doctoral student who co-authored the study.

Men concerned about their fertility may wonder what foods contain DHA. Marine fish, such as salmon or tuna, are excellent sources of this omega-3 fatty acid.

The scientists became intrigued with DHA’s role in creating healthy sperm when they experimented with “knockout” mice that lack a gene essential to its synthesis. “We looked at sperm count, shape, and motility, and tested the breeding success rate. The male mice that lacked DHA were basically infertile,” Nakamura said.

But when DHA was introduced into the mice’s diet, fertility was completely restored. “It was very striking. When we fed the mice DHA, all these abnormalities were prevented,” he said.

The scientists then used confocal laser scanning (3D) microscopy to look at thin slices of tissue in progressive stages of a sperm cell’s development. By labeling enzymes with fluorescence, they could track their location in a cell.

“We could see that the acrosome is constructed when small vesicles containing enzymes fuse together in an arc. But that fusion doesn’t happen without DHA,” he said.

In the absence of DHA, the vesicles are formed but they don’t come together to make the arch that is so important in sperm cell structure, he noted.

Nakamura finds the role this omega-3 fatty acid plays in membrane fusion particularly exciting. Because DHA is abundant in specific tissues, including the brain and the retina as well as the testes, the scientists believe their research findings could also impact research relating to brain function and vision.

“It’s logical to hypothesize that DHA is involved in vesicle fusion elsewhere in the body, and because the brain contains so much of it, we wonder if deficiencies could play a role, for example, in the development of dementia. Any communication between neurons in the brain involves vesicle fusion,” he noted.

The Illinois scientists will continue to study sperm; meanwhile, Nakamura has sent some of his DHA-deficient knockout mice to other laboratories where scientists are studying DHA function in the brain and the retina.

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The study was published in a recent issue of Biology of Reproduction. Co-authors are Manuel Roqueta-Rivera, Timothy L. Abbott, Mayandi Sivaguru, and Rex A. Hess, all of the U of I. The work was supported in part by a CONACyT Mexico fellowship award.

Quick-Cooking Nanomaterials in Microwave to Make Tomorrow's Air Conditioners

Engineering researchers at Rensselaer Polytechnic Institute have developed a new method for creating advanced nanomaterials that could lead to highly efficient refrigerators and cooling systems requiring no refrigerants and no moving parts. The key ingredients for this innovation are a dash of nanoscale sulfur and a normal, everyday microwave oven. (Credit: Image courtesy of Rensselaer Polytechnic Institute)

Science Daily — Engineering researchers at Rensselaer Polytechnic Institute have developed a new method for creating advanced nanomaterials that could lead to highly efficient refrigerators and cooling systems requiring no refrigerants and no moving parts. The key ingredients for this innovation are a dash of nanoscale sulfur and a normal, everyday microwave oven.

Rensselaer Professor Ganpati Ramanath led the study, in collaboration with colleagues Theodorian Borca-Tasciuc and Richard W. Siegel.At the heart of these solid-state cooling systems are thermoelectric materials, which can convert electricity into a range of different temperatures -- from hot to cold. Thermoelectric refrigerators employing these principles have been available for more than 20 years, but they are still small and highly inefficient. This is largely because the materials used in current thermoelectric cooling devices are expensive and difficult to make in large quantities, and do not have the necessary combination of thermal and electrical properties. A new study, recently published in the journal Nature Materials, overcomes these challenges and opens the door to a new generation of high-performance, cost-effective solid state refrigeration and air conditioning.

Driving this research breakthrough is the idea of intentionally contaminating, or doping, nanostructured thermoelectric materials with barely-there amounts of sulfur. The doped materials are obtained by cooking the material and the dopant together for few minutes in a store-bought $40 microwave oven. The resulting powder is formed into pea-sized pellets by applying heat and pressure in a way that preserves the properties endowed by the nanostructuring and the doping. These pellets exhibit properties better than the hard-to-make thermoelectric materials currently available in the marketplace. Additionally, this new method for creating the doped pellets is much faster, easier, and cheaper than conventional methods of making thermoelectric materials.

"This is not a one-off discovery. Rather, we have developed and demonstrated a new way to create a whole new class of doped thermoelectric materials with superior properties," said Ramanath, a faculty member in the Department of Materials Science and Engineering at Rensselaer. "Our findings truly hold the potential to transform the technology landscape of refrigeration and make a real impact on our lives." 

Trying to engineer thermoelectric materials is somewhat like playing a game of "tug of war," Ramanath said. Researchers endeavor to control three separate properties of the material: electrical conductivity, thermal conductivity, and Seebeck coefficient. Manipulating one of these properties, however, necessarily affects the other two. This new study demonstrates a new way to minimize the interdependence of these three properties by combining doping and nanostructuring in well-known thermoelectric materials such as tellurides and selenides based on bismuth and antimony.

The goal of tweaking these three properties is to create a thermoelectric material with a high figure of merit, or ZT, which is a measure of how efficient the material is at converting heat to electricity. The new pea-sized pellets of nanomaterials developed by the Rensselaer team demonstrated a ZT of 1 to 1.1 at room temperature. Since such high values are obtained even without optimizing the process, the researchers are confident that higher ZT can be obtained with some smart engineering.

"It's really amazing as to how nanostructures seasoned with just a few atoms of sulfur can lead to such superior thermoelectric properties of the bulk material made from the nanostructures, and allows us to reap the benefits of nanostructuring on a macroscale," Ramanath said.

An important facet of the discovery is the ability to make both p-type (positive charge) and n-type (negative charge) thermoelectric nanomaterials with a high ZT. Up until now, researchers around the world have only been able to make large quantities of p-type materials with high ZT.

Additionally, the new study shows the Rensselaer research team can make batches of 10 to 15 grams (enough to make several pea-sized pellets) of the doped nanomaterial in two to three minutes with a microwave oven. Larger quantities can be produced using industrial-sized microwaves ovens.

"Our ability to scalably and inexpensively produce both p- and n-type materials with a high ZT paves the way to the fabrication of high-efficiency cooling devices, as well as solid-state thermoelectric devices for harvesting waste heat or solar heat into electricity," said Borca-Tasciuc, professor in the Department of Mechanical, Aerospace, and Nuclear Engineering at Rensselaer.

"This is a very exciting discovery because it combines the realization of novel and useful thermoelectric properties with a demonstrated processing route forward to industrial applications," said Siegel, the Robert W. Hunt Professor of Materials Science and Engineering at Rensselaer.

Rensselaer graduate student Rutvik J. Mehta carried out this work for his doctoral thesis. Mehta, Ramanath, and Borca-Tasciuc have filed a patent and formed a new company, ThermoAura Inc., to further develop and market the new thermoelectric materials technology. Mehta has since graduated and is now a post-doctoral associate at Rensselaer. He also serves as president of ThermoAura.

Beyond refrigerators and air conditioning, the researchers envision this technology could one day be used to cool computer chips.

Along with Ramanath,Borca-Tasciuc, Siegel, and Mehta, co-authors of the paper are Rensselaer graduate students Yanliang Zhang, Chinnathambi Karthik, and Binay Singh.

This research is funded by support from the National Science Foundation (NSF); IBM through the Rensselaer Nanotechnology Center; and the U.S. Department of Energy through the S³TEC Energy Frontiers Research Center at the Massachusetts Institute of Technology (MIT).

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Molecular 'Culprit' in Rise of Planetary Oxygen

University of Illinois crop sciences and Institute for Genomic Biology professor Gustavo Caetano-Anollés and his colleagues identified an oxygen-generating enzyme that likely was a key contributor to the rise of molecular oxygen on earth. (Credit: L. Brian Stauffer)                                                          Science Daily  — A turning point in the history of life occurred 2 billion to 3 billion years ago with the unprecedented appearance and dramatic rise of molecular oxygen. Now researchers report they have identified an enzyme that was the first -- or among the first -- to generate molecular oxygen on Earth.

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The new findings, reported in the journal Structure, build on more than a dozen previous studies that aim to track the molecular evolution of life by looking for evidence of that history in present-day protein structures. These studies, led by University of Illinois crop sciences and Institute for Genomic Biology professor Gustavo Caetano-Anollés, focus on structurally and functionally distinct regions of proteins -- called folds -- that are part of the universal toolkit of living cells.

Protein folds are much more stable than the sequences of amino acids that compose them, Caetano-Anollés said. Mutations or other changes in sequence often occur without disrupting fold structure or function. This makes folds much more reliable markers of long-term evolutionary patterns, he said.

In the new study, Caetano-Anollés, working with colleagues in China and Korea, tackled an ancient mystery: Why did some of the earliest organisms begin to generate oxygen, and why?

"There is a consensus from earth scientists that about 2.4 billion years ago there was a big spike in oxygen on Earth," Caetano-Anollés said. They generally agree that this rise in oxygen, called the Great Oxygenation Event, was tied to the emergence of photosynthetic organisms.

"But the problem now comes with the following question," he said. "Oxygen is toxic, so why would a living organism generate oxygen? Something must have triggered this."

The researchers looked for answers in the "molecular fossils" that still reside in living cells. They analyzed protein folds in nearly a thousand organisms representing every domain of life to assemble a timeline of protein history. Their timeline for this study was limited to single-fold proteins (which the researchers believe are the most ancient), and was calibrated using microbial fossils that appeared in the geologic record at specific dates.

The analysis revealed that the most ancient reaction of aerobic metabolism involved synthesis of pyridoxal (the active form of vitamin B6, which is essential to the activity of many protein enzymes) and occurred about 2.9 billion years ago. An oxygen-generating enzyme, manganese catalase, appeared at the same time.

Other recent studies also suggest that aerobic (oxygen-based) respiration began on Earth 300 to 400 million years before the Great Oxidation Event, Caetano-Anollés said. This would make sense, since oxygen production was probably going on for a while before the spike in oxygen occurred.

Catalases convert hydrogen peroxide to water and oxygen. The researchers hypothesize that primordial organisms "discovered" this enzyme when trying to cope with an abundance of hydrogen peroxide in the environment. Some geochemists believe that hydrogen peroxide was abundant at this time as a result of intensive solar radiation on glaciers that covered much of Earth.

"In the glacial melt waters you would have a high concentration of hydrogen peroxide and that would be gradually exposing a number of the primitive organisms (alive at that time)," Caetano-Anollés said. The appearance of manganese catalase, an enzyme that degrades hydrogen peroxide and generates oxygen as a byproduct, makes it a likely "molecular culprit for the rise of oxygen on the planet," he said.

The research team included scientists from the Korea Research Institute of Bioscience and Biotechnology; Huazhong Agricultural University, China; and Shandong University of Technology, China.

Rare Ultra-Blue Stars Found in Neighboring Galaxy's Hub

The image at left shows the nearby, majestic Andromeda galaxy. The rectangular box marks the region probed by NASA's Hubble Space Telescope. Hubble's view, taken with the Wide Field Camera 3 and the Advanced Camera for Surveys, is shown in the images on the right. The images are a blend of visible and ultraviolet light. The photo at top right is 7,900 light-years across and reveals the galaxy's crowded central region. The bright area near the center of the image is a grouping of stars nestled around the galaxy's black hole. The blue dots sprinkled throughout the image are ultra-blue stars whose population increases around the crowded hub. The blue stars are old Sun-like stars that have prematurely cast off their outer layers of material, exposing their extremely blue-hot cores. The square box outlines a close-up view of an area around the core. The detailed image, shown at bottom right, reveals a richer population of blue stars huddled around the core. Dark dust clouds also are visible. The image is 740 light-years wide. (Credit: NASA, ESA, B.F. Williams (University of Washington, Seattle), D. Lang (Princeton University, N.J.), J. Kalirai (Space Telescope Science Institute, Baltimore), and J. Dalcanton (University of Washington, Seattle))                                                             Science Daily — Peering deep inside the hub of the neighboring Andromeda galaxy, NASA's Hubble Space Telescope has uncovered a large, rare population of hot, bright stars.

Astronomers were surprised when they spotted these stars because physical models show that only an unusual type of old star can be as hot and as bright in ultraviolet light.Blue is typically an indicator of hot, young stars. In this case, however, the stellar oddities are aging, Sun-like stars that have prematurely cast off their outer layers of material, exposing their extremely blue-hot cores.

While Hubble has spied these ultra-blue stars before in Andromeda, the new observation covers a much broader area, revealing that these stellar misfits are scattered throughout the galaxy's bustling center. Astronomers used Hubble's Wide Field Camera 3 to find roughly 8,000 of the ultra-blue stars in a stellar census made in ultraviolet light, which traces the glow of the hottest stars. The study is part of the multi-year Panchromatic Hubble Andromeda Treasury survey to map stellar populations across the Andromeda galaxy.

"We were not looking for these stars. They stood out because they were bright in ultraviolet light and very different from the stars we expected to see," said Julianne Dalcanton of the University of Washington in Seattle, leader of the Hubble survey.

The team's results are being presented January 11 at the American Astronomical Society meeting in Austin, Texas.

The telescope spied the stars within 2,600 light-years of Andromeda's core. After analyzing the stars for nearly a year, Dalcanton's team determined that they were well past their prime. "The stars are dimmer and have a range of surface temperatures different from the extremely bright stars we see in the star-forming regions of Andromeda," said team member Phil Rosenfield of the University of Washington.

As these stars evolved, puffing up to become red giants, they ejected most of their outer layers to expose their blue-hot cores. When normal Sun-like stars swell up to become red giants, they lose much less material and therefore never look as bright in the ultraviolet.

"We caught these stars when they're the brightest, just before they become white dwarfs," said team member Leo Girardi of the National Institute for Astrophysics's Astronomical Observatory of Padua. "It is likely that there are many other similarly hot stars in this central part of Andromeda at earlier stages of their lives. But such stars are too dim for Hubble to see because they're mixed in with a crowd of normal stars."

The astronomers have proposed two possible scenarios to explain why these blue stars evolve differently. According to Rosenfield, the most likely scenario is that the stars are rich in chemical elements other than hydrogen and helium. Observations with ground-based telescopes have shown the stars in the galaxy's hub have an abundant supply of "heavy elements," which makes it easier for stars to eject lots of material into space late in life.

In this scenario radiation from the star is more efficient at pushing on gas laced with heavy elements, which drives away the material, like wind moving a thick sail. Although all the stars in the core are enriched in heavy elements, the bright blue stars may contain especially high amounts, which help trigger the mass loss.

The study also shows that the number of blue stars decreases with distance from the core, tracing the drop in the amount of heavy elements.

Another possible explanation is that the blue stars are in close binary systems and have lost mass to their partners. This mass loss would expose the stars' hot cores. The astronomers were surprised to find that the ultra-blue stars are distributed in the galaxy in the same way as a population of binary stars with similar masses that were found in X-ray observations by NASA's Chandra X-ray Observatory.

The astronomers' next step is to create simulations of these stars to try to determine which scenario is the one that leads them on a different evolutionary path.

Can One Phone Save Nokia and Microsoft? Nokia Lumia 900 - first hands-on video

The Lumia 900 is Nokia's attempt to draw level with Apple and Google and also carries the hopes of Microsoft.

• BY TOM SIMONITE

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Battle plan: Nokia's CEO Steven Elop announces the Lumia 900 at CES in Las Vegas.
Technology Review

It's blue, plastic, and could decide the fate of two multibillion-dollar companies. 

The Lumia 900 was launched by Finnish phone company Nokia at the Consumer Electronics Show in Las Vegas today with surprisingly frank talk from the company's CEO about how both his company and Microsoft trail in the market for smart phones.

Steven Elop repeatedly drew on military metaphors to describe how he planned to assault the U.S. market. "Clearly there are strong contenders already on the field, [and] our strategy has been to establish a series of beachheads," he said, before unveiling the new handset, which comes in either black or cyan, and will be available on AT&T's 4G network in coming weeks. "From that beachhead, you will see us push forward," said Elop.

The warhorse leading that charge, the Lumia 900, is an LTE device with a polycarbonate plastic case. It has a 4.3-inch screen with an OLED display that Nokia nicknames "clear black" and uses a technology unique to the company to deliver truer blacks than most OLED displays, said Elop. The phone's camera offers a wider angle of view than most smart phones, said Nokia senior vice president Kevin Shields while demonstrating the device on stage. He also boasted about the camera's large aperture, which means it lets more light reach its sensor. "The front camera lets in as much light as the back camera on pretty much any other smart phone out there," said Shields. The price for the Lumia was not announced, but Elop claimed it would be "competitive."

Nokia's partner of just one year, Microsoft, has as much riding on the Lumia 900 as Nokia does, as underlined by the surprise appearance of Microsoft CEO Steve Ballmer on stage with Elop. He underlined the commitment of the two companies to one another, one that cynics might say is due to the fact that each has nowhere else to go.

At the time of the agreement between the two companies, Nokia found itself without a smart phone operating system able to punch its weight against those of Apple and Google. Microsoft had just reinvented its struggling mobile operating system but faced an uphill battle turning the heads of phone manufacturers, such as Samsung and HTC, that had enthusiastically embraced Google's Android operating system.

"We didn't sign a contract to work together until less than a year ago," said Ballmer. "To go from concept and discussion to real engineering partnership to delivery is fantastic." He went on to call the Lumia 900 an "incredibly important milestone" before acknowledging that Windows Phone is far from on par with its competitors. "There's a lot of room to grow in terms of selling Windows phones," said Ballmer. "This third ecosystem is really going to pay off for users, for developers, for operators, and I trust for our two companies." There are now more than 50,000 apps available for Windows Phone, said Ballmer. Apple currently states that there are more than 500,000 apps for the iPhone, while Google said in October that there are over 400,000 for Android phones.

Latest model: The Lumia 900.
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Elop claimed that Windows Phone provided a genuine alternative to models pushed by Apple and Google's mobile operating systems, which share basic design features like the way apps appear as icons. "The product itself has to stand for something, it has to be differentiated," said Elop, praising the "live tiles" of Windows Phone. The tiles are both shortcuts to apps and also notification areas that can show things like Facebook activity and Twitter messages. That design is much more valuable, said Elop, than "yet another collection of static applications on a grid."

He conceded that Nokia would have to make efforts to communicate that to consumers more familiar with Apple and Google's offerings, saying that 2012 would see the company spend money on that. Such is Nokia's need to see Windows Phone charm consumers that Elop even said he welcomed competition from other companies launching phones with that operating system. "I'm happy that Samsung and others are introducing Windows devices, because our principal competition is other ecosystems," said Elop.

Asked whether Nokia would release tablet computers, perhaps based on Microsoft's forthcoming Windows 8, Elop said that it would depend on being able to offer something different from existing tablets. "You want to ensure differentiation, as we have for phones, with camera optics, design, and the operating system," he said. "If we believe we can bring differentiation to tablets, whatever it may be, then clearly, it's an opportunity for Nokia."