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A number of quantum theorists and cosmologists are trying to figure out whether our universe is part of a bigger "multiverse." But others suspect that this hard-to-test idea may be a question for philosophers.

In the first moments after the big bang, the universe blew up at an incredible rate. But what did the blowing? Measurements of the cosmic microwave background and other astrophysical observations are narrowing the possibilities.

The broad brush strokes are visible, but the fine details aren't. Data from satellites and ground-based telescopes may soon help pinpoint, among other particulars, when the first generation of stars burned off the hydrogen "fog" that filled the universe.

Above a certain energy, cosmic rays don't travel very far before being destroyed. So why are cosmic ray hunters spotting such rays with no obvious source within our galaxy?

The mightiest energy fountains in the universe probably get their power from matter plunging into whirling supermassive black holes. But the details of what drives their jets remain anybody's guess.

Relativistic mass crammed into a quantum-sized object? It's a recipe for disaster--and scientists are still trying to figure out the ingredients.

To a particle physicist, matter and antimatter are almost the same. Some subtle difference must explain why matter is common and antimatter rare.

In a theory of everything, quarks (which make up protons) should somehow be convertible to leptons (such as electrons)--so catching a proton decaying into something else might reveal new laws of particle physics.

It clashes with quantum theory. It doesn't fit in the Standard Model. Nobody has spotted the particle that is responsible for it. Newton's apple contained a whole can of worms.

It took millennia for scientists to realize that time is a dimension, like the three spatial dimensions, and that time and space are inextricably linked. The equations make sense, but they don't satisfy those who ask why we perceive a "now" or why time seems to flow the way it does.

Atoms were "uncuttable." Then scientists discovered protons, neutrons, and other subatomic particles- which were, in turn, shown to be made up of quarks and gluons. Is there something more fundamental still?

Nobody knows this basic fact about neutrinos, although a number of underground experiments are under way. Answering this question may be a crucial step to understanding the origin of matter in the universe.

High-temperature superconductors and materials with giant and colossal magnetoresistance are all governed by the collective rather than individual behavior of electrons. There is currently no common framework for understanding them.

Theorists say an intense enough laser field would rip photons into electron-positron pairs, dousing the beam. But no one knows whether it's possible to reach that point.

They've done it with microwaves but never with visible light.

Such devices have been demonstrated at low temperatures but not yet in a range warm enough for spintronics applications.

Electrons in superconductors surf together in pairs. After 2 decades of intense study, no one knows what holds them together in the complex, high-temperature materials.

So far, such "nonequilibrium systems" defy the tool kit of statistical mechanics, and the failure leaves a gaping hole in physics.

A superheavy element with 184 neutrons and 114 protons should be relatively stable, if physicists can create it.

Despite hints in solid helium, nobody is sure whether a crystalline material can flow without resistance. If new types of experiments show that such outlandish behavior is possible, theorists would have to explain how.

Researchers continue to tussle over how many bonds each H2O molecule makes with its nearest neighbors.

Molecules in a glass are arranged much like those in liquids but are more tightly packed. Where and why does liquid end and glass begin?

The larger synthetic molecules get, the harder it is to control their shapes and make enough copies of them to be useful. Chemists will need new tools to keep their creations growing.

Conventional solar cells top out at converting 32% of the energy in sunlight to electricity. Can researchers break through the barrier?

It's been 35 years away for about 50 years, and unless the international community gets its act together, it'll be 35 years away for many decades to come.

Scientists believe differing rates of rotation from place to place on the sun underlie its 22-year sunspot cycle. They just can't make it work in their simulations. Either a detail is askew, or it's back to the drawing board.

How bits of dust and ice and gobs of gas came together to form the planets without the sun devouring them all is still unclear. Planetary systems around other stars should provide clues.

Something about the way the planet tilts, wobbles, and careens around the sun presumably brings on ice ages every 100,000 years or so, but reams of climate records haven't explained exactly how.

Computer models and laboratory experiments are generating new data on how Earth's magnetic poles might flip-flop. The trick will be matching simulations to enough aspects of the magnetic field beyond the inaccessible core to build a convincing case.

Prospects for finding signs of an imminent quake have been waning since the 1970s. Understanding faults will progress, but routine prediction would require an as-yet-unimagined breakthrough.

The search for life--past or present--on other planetary bodies now drives NASA's planetary exploration program, which focuses on Mars, where water abounded when life might have first arisen.

Most biomolecules can be synthesized in mirror-image shapes. Yet in organisms, amino acids are always left-handed, and sugars are always right-handed. The origins of this preference remain a mystery.

Out of a near infinitude of possible ways to fold, a protein picks one in just tens of microseconds. The same task takes 30 years of computer time.

It has been hard enough counting genes. Proteins can be spliced in different ways and decorated with numerous functional groups, all of which makes counting their numbers impossible for now.

Protein-protein interactions are at the heart of life. To understand how partners come together in precise orientations in seconds, researchers need to know more about the cell's biochemistry and structural organization.

In the 1970s, apoptosis was finally recognized as distinct from necrosis. Some biologists now argue that the cell death story is even more complicated. Identifying new ways cells die could lead to better treatments for cancer and degenerative diseases.

Membranes inside cells transport key nutrients around, and through, various cell compartments without sticking to each other or losing their way. Insights into how membranes stay on track could help conquer diseases, such as cystic fibrosis.

Centrosomes, which help pull apart paired chromosomes, and other organelles replicate on their own time, without DNA's guidance. This independence still defies explanation.

RNA is turning out to play a dizzying assortment of roles, from potentially passing genetic information to offspring to muting gene expression. Scientists are scrambling to decipher this versatile molecule.

These chromosome features will remain mysteries until new technologies can sequence them.

The puffer fish genome is 400 million bases; one lungfish's is 133 billion bases long. Repetitive and duplicated DNA don't explain why this and other size differences exist.

DNA between genes is proving important for genome function and the evolution of new species. Comparative sequencing, microarray studies, and lab work are helping genomicists find a multitude of genetic gems amid the junk.

New tools and conceptual breakthroughs are driving the cost of DNA sequencing down by orders of magnitude. The reductions are enabling research from personalized medicine to evolutionary biology to thrive.

A person's right and left legs almost always end up the same length, and the hearts of mice and elephants each fit the proper rib cage. How genes set limits on cell size and number continues to mystify.

Researchers are finding ever more examples of this process, called epigenetics, but they can't explain what causes and preserves the changes.

Whirling cilia help an embryo tell its left from its right, but scientists are still looking for the first factors that give a relatively uniform ball of cells a head, tail, front, and back.

The genes that determine the length of a nose or the breadth of a wing are subject to natural and sexual selection. Understanding how selection works could lead to new ideas about the mechanics of evolution with respect to development.

Nutrition--including that received in utero--seems to help set this mysterious biological clock, but no one knows exactly what forces childhood to end.

The most aggressive cancer cells look a lot like stem cells. If cancers are caused by stem cells gone awry, studies of a cell's "stemness" may lead to tools that could catch tumors sooner and destroy them more effectively.

Although our immune responses can suppress tumor growth, tumor cells can combat those responses with counter-measures. This defense can stymie researchers hoping to develop immune therapies against cancer.

Drugs that cut off a tumor's fuel supplies--say, by stopping blood-vessel growth--can safely check or even reverse tumor growth. But how long the drugs remain effective is still unknown.

It's a driver of arthritis, but cancer and heart disease? More and more, the answer seems to be yes, and the question remains why and how.

Even if one accepts that prions are just misfolded proteins, many mysteries remain. How can they go from the gut to the brain, and how do they kill cells once there, for example.

This system predates the vertebrate adaptive immune response. Its relative importance is unclear, but immunologists are working to find out.

Yes, say a few prominent thinkers, but experiments with mice now challenge the theory. Putting the debate to rest would require proving that something is not there, so the question likely will not go away.

Recent evidence suggests that the mother's immune system doesn't "realize" that the fetus is foreign even though it gets half its genes from the father. Yet just as Nobelist Peter Medawar said when he first raised this question in 1952, "the verdict has yet to be returned."

Circadian clock genes have popped up in all types of creatures and in many parts of the body. Now the challenge is figuring out how all the gears fit together and what keeps the clocks set to the same time.

Birds, butterflies, and whales make annual journeys of thousands of kilometers. They rely on cues such as stars and magnetic fields, but the details remain unclear.

A sound slumber may refresh muscles and organs or keep animals safe from dangers lurking in the dark. But the real secret of sleep probably resides in the brain, which is anything but still while we're snoring away.

Freud thought dreaming provides an outlet for our unconscious desires. Now, neuroscientists suspect that brain activity during REM sleep--when dreams occur--is crucial for learning. Is the experience of dreaming just a side effect?

Monitoring brain activity in young children--including infants—may shed light on why children pick up languages with ease while adults often struggle to learn train station basics in a foreign tongue.

Many animals use airborne chemicals to communicate, particularly when mating. Controversial studies have hinted that humans too use pheromones. Identifying them will be key to assessing their sway on our social lives.

Scientists are chipping away at the drugs' effects on individual neurons, but understanding how they render us unconscious will be a tougher nut to crack.

Researchers are trying to track down genes involved in this disorder. Clues may also come from research on traits schizophrenics share with normal people.

Many genes probably contribute to this baffling disorder, as well as unknown environmental factors. A biomarker for early diagnosis would help improve existing therapy, but a cure is a distant hope.

A 5- to 10-year delay in this late-onset disease would improve old age for millions. Researchers are determining whether treatments with hormones or antioxidants, or mental and physical exercise, will help.

Addiction involves the disruption of the brain's reward circuitry. But personality traits such as impulsivity and sensation-seeking also play a part in this complex behavior.

That question has long puzzled philosophers; now some neuroscientists think brain imaging will reveal circuits involved in reasoning.

Computers can already beat the world's best chess players, and they have a wealth of information on the Web to draw on. But abstract reasoning is still beyond any machine.

Aspects of personality are influenced by genes; environment modifies the genetic effects. The relative contributions remain under debate.

Much of the "environmental" contribution to homosexuality may occur before birth in the form of prenatal hormones, so answering this question will require more than just the hunt for "gay genes."

Despite better morphological, molecular, and statistical methods, researchers' trees don't agree. Expect greater, but not complete, consensus.

Count all the stars in the sky? Impossible. Count all the species on Earth? Ditto. But the biodiversity crisis demands that we try.

A "simple" concept that's been muddied by evolutionary data; a clear definition may be a long time in coming.

Once considered rare, gene swapping, particularly among microbes, is proving quite common. But why and how genes are so mobile--and the effect on fitness--remains to be determined.

Ideas about the origin of the 1.5-billion-year-old "mother" of all complex organisms abound. The continued discovery of primitive microbes, along with comparative genomics, should help resolve life's deep past.

Darwin called this question an "abominable mystery." Flowers arose in the cycads and conifers, but the details of their evolution remain obscure.

Cellulose and pectin walls surround cells, keeping water in and supporting tall trees. The biochemistry holds the secrets to turning its biomass into fuel.

Redwoods grow to be hundreds of meters tall, Arctic willows barely 10 centimeters. Understanding the difference could lead to higher-yielding crops.

Plants can mount a general immune response, but they also maintain molecular snipers that take out specific pathogens. Plant pathologists are asking why different species, even closely related ones, have different sets of defenders. The answer could result in hardier crops.

We need crops that better withstand drought, cold, and other stresses. But there are so many genes involved, in complex interactions, that no one has yet figured out which ones work how.

A huge impact did in the dinosaurs, but the search for other catastrophic triggers of extinction has had no luck so far. If more subtle or stealthy culprits are to blame, they will take considerably longer to find.

Finding cost-effective and politically feasible ways to save many endangered species requires creative thinking.

Dinosaurs reached almost unimaginable sizes, some in less than 20 years. But how did the long-necked sauropods, for instance, eat enough to pack on up to 100 tons without denuding their world?

To anticipate the effects of the intensifying greenhouse, climate modelers will have to focus on regional changes and ecologists on the right combination of environmental changes.

The new dwarf human species fossil from Indonesia suggests that at least four kinds of humans thrived in the past 100,000 years. Better dates and additional material will help confirm or revise this picture.

Did Homo sapiens acquire abstract thought, language, and art gradually or in a cultural "big bang," which in Europe occurred about 40,000 years ago? Data from Africa, where our species arose, may hold the key to the answer.

No animal comes close to having humans' ability to build on previous discoveries and pass the improvements on. What determines those differences could help us understand how human culture evolved.

Neuroscientists exploring how we speak and make music are just beginning to find clues as to how these prized abilities arose.

Anthropologists have long argued that race lacks biological reality. But our genetic makeup does vary with geographic origin and as such raises political and ethical as well as scientific questions.

From Norway to Nigeria, living standards across countries vary enormously, and they're not becoming more equal.

The United States could provide a test case.

China may provide one answer.

Almost all efforts to reduce poverty in sub-Saharan Africa have failed. Figuring out what will work is crucial to alleviating massive human suffering. The following six mathematics questions are drawn from a list of seven outstanding problems selected by the Clay Mathematics Institute. (The seventh problem is discussed on p. 96.) For more details, go to www.claymath.org/millennium.

Equations of the form y2 = x3 ax b are powerful mathematical tools. The Birch and Swinnerton-Dyer conjecture tells how to determine how many solutions they have in the realm of rational numbers information that could solve a host of problems, if the conjecture is true.

Two useful mathematical structures arose independently in geometry and in abstract algebra. The Hodge conjecture posits a surprising link between them, but the bridge remains to be built.

First written down in the 1840s, the equations hold the keys to understanding both smooth and turbulent flow. To harness them, though, theorists must find out exactly when they work and under what conditions they break down.

You can tie a string around a doughnut, but it will slide right off a sphere. The mathematical principle behind that observation can reliably spot every spherelike object in 3D space. Henri Poincaré conjectured that it should also work in the next dimension up, but no one has proved it yet.

Don't sweat the details. Since the mid-19th century, the "Riemann hypothesis" has been the monster catfish in mathematicians' pond. If true, it will give them a wealth of information about the distribution of prime numbers and other long-standing mysteries.

For almost 50 years, the model has rested on "quantum Yang-Mills theory," which links the behavior of particles to structures found in geometry. The theory is breathtakingly elegant and useful--but no one has proved that it's sound.