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Since talks in Moscow last June, Iran has continued to increase its stockpile of uranium enriched to 20 percent purity, has begun to install a new generation of centrifuges and has not yet completed an agreement on inspection of suspect military sites with the International Atomic Energy Agency, a deal originally advertised as all but done last May.

With presidential elections in Iran scheduled for June, senior Western diplomats involved with these talks expressed skepticism that Tehran's chief negotiator, Saeed Jalili, would be willing to make compromises that could be portrayed as weakness at home.

Mr. Jalili is the personal representative of Iran's supreme leader, Ayatollah Ali Khamenei, considered the dominant voice on the nuclear issue. Ayatollah Khamenei has recently expressed continued mistrust of the United States and its intentions, saying that he would not allow the kind of bilateral talks between Washington and Tehran that most analysts think would be crucial to any resolution.

At the same time, Iran has taken some of its stockpile of 20 percent enriched uranium and converted it into reactor fuel, which cannot easily be turned back. The conversion means that Iran now has less of the uranium needed to make a bomb, reducing the sense of urgency among the six powers, and Israel, that its nuclear program needs to be slowed.

But the total Iranian stockpile of 20 percent enriched uranium has nonetheless grown since November to 167 kilograms from 135 kilograms, according to the most recent I.A.E.A. report — closer to, if still significantly below, the 240 kilograms or 250 kilograms many experts consider necessary, once enriched further, to produce a nuclear weapon.

Iran denies that its nuclear program has any military aim. The six world powers, the so-called P5-plus-1 group, which are the five permanent members of the United Nations Security Council — Britain, China, France, Russia and the United States — and Germany, want Iran to obey Security Council resolutions ordering it to suspend enrichment and open itself up fully to I.A.E.A. inspectors, to ensure that there is no effort to build a nuclear weapon.

To press Iran to comply, the Security Council, the United States and the European Union have created an increasingly painful set of economic sanctions on Iran, as part of a dual-track strategy — negotiations and sanctions. Iran has for its part insisted that as a precondition for serious negotiations, the world should lift all the sanctions and recognize Iran's "right to enrich," which Iran asserts it has as a signatory to the Nuclear Nonproliferation Treaty.

The negotiations have been tedious, with Iran appearing to be playing for time, diplomats say. The six powers had asked for a resumption of these talks as early as December, but Iran rejected dates and sites before finally suggesting and agreeing upon Almaty. The choice pleased Western diplomats for its symbolic value, since Kazakhstan, when it became independent of the Soviet Union, freely relinquished the nuclear weapons it had inherited from Moscow. American officials are holding up Kazakhstan, one of the world's largest producers of uranium and a maker of nuclear fuel, as an example to Iran of the benefits of peaceful nuclear energy and compliance with the I.A.E.A.

President Nursultan Nazarbayev of Kazakhstan appealed to Tehran in a New York Times Op-Ed article in March 2012 to abandon what he suggested was its pursuit of nuclear power status. "Kazakhstan's experience shows that nations can reap huge benefits from turning their backs on nuclear weapons," he wrote.

While expectations are low, the six hope to leave here with some momentum and signs of Iranian willingness to engage in what all have agreed should be a reciprocal and step-by-step process of lifting sanctions in return for Iranian actions to comply.

"Iran needs to understand that there is an urgent need to make concrete and tangible progress" in these talks, said Michael Mann, the spokesman for Catherine Ashton, the European Union's foreign policy chief and chairwoman of the P5-plus-1 group.

Mr. Mann said that the six powers have together "prepared a good and updated offer for the talks which we believe is balanced and a fair basis for constructive talks" and that is "also responsive to Iranian ideas."

He and other Western diplomats refused to detail the offer before it is presented to the Iranians, but one senior diplomat called the offer "substantial and serious" and said recent news reports that suggested only some loosening in sanctions regarding gold sales "do not reflect the full offer." The diplomat said the offer was "not a big bang deal, more an agreement on a package of confidence-building measures."

"Our main concern is the enrichment over 5 percent," which brings uranium closer to becoming bomb-grade, he said. "Iran has a great deal to gain by engaging. Once the international community has the assurances it needs, sanctions will start to be lifted."

Another Western diplomat said that the offer was updated to account for the new enrichment Iran has done in the eight months since Moscow. There, the offer was described as "stop, shut, ship" — demanding that Iran stop enrichment of uranium to 20 percent purity, shut the Fordow underground enrichment facility that is heavily protected deep inside a mountain, and ship abroad its stockpile of 20 percent enriched uranium to be turned into nuclear fuel.

In response, the six said in Moscow that they would reciprocate initially by lifting some sanctions, including on parts for American civilian aircraft that Iran has long sought, and provide fuel for an Iranian nuclear reactor.

The sanctions have hurt the Iranian economy, especially the sanctions on oil exports, which make up a large part of the economy. French officials say that Iran's annual economic output has fallen by 8 percent because of the sanctions, inflation is very high — officially at 27. 4 percent in 2012 but unofficially much higher — and the value of the Iranian currency, the rial, has dropped by about half over the past year.

While Iranian officials insist that their economy is resilient, a senior American official said: "They're beginning to feel the pressure of the sanctions."

As for Iran's presidential elections in June, the American official acknowledged that the vote "may constrain their political space," but said that the nuclear negotiations had their own pace, which the six would like to accelerate. "We all understand that when it comes to the nuclear file, the key decisions are in the hands of the supreme leader," the official said, referring to Ayatollah Khamenei. "And he is not going to change."

In more than a century of scientific inquiry into the interwoven cells known as neurons that make up the brain, researchers acknowledge they are only beginning to scratch the surface of a scientific challenge that is certain to prove vastly more complicated than sequencing the human genome.

The Obama administration is hoping to announce as soon as next month its intention to assemble the pieces — and, even more challenging, the financing — for a decade-long research project that will have the goal of building a comprehensive map of the brain's activity.

At present, scientists are a long way from doing so. Before they can even begin the process, they have to develop the tools to examine the brain. And before they develop tools that will work on humans, they must succeed in doing so in a number of simpler species — assuming that what they learn can even be applied to humans.

Besides the technological and scientific challenges, there are a host of issues involving storing the information researchers gather, and ethical concerns about what can be done with the data. Also highly uncertain is whether the science will advance quickly enough to meet the time frames being considered for what is being called the Brain Activity Map project.

Many neuroscientists are skeptical that a multiyear, multibillion dollar effort to unlock the brain's mysteries will succeed."I believe the scientific paradigm underlying this mapping project is, at best, out of date and at worst, simply wrong," said Donald G. Stein, a neurologist at the Emory University School of Medicine in Atlanta. "The search for a road map of stable, neural pathways that can represent brain functions is futile."

The state of the art in animal research is to sample from roughly a thousand neurons simultaneously. The human brain has between 85 and 100 billion neurons. "For a human we must develop new techniques, and some of them from scratch," said Dr. Rafael Yuste, a neuroscientist at Columbia who has pioneered the use of lasers to measure the activity of neurons in the cortex of mice.

An article last year in the journal Neuron described a possible path toward mapping the active human brain. The article, signed by six prominent scientists, proposes that the project begin with species that have brains with very small numbers of neurons and then work toward increasingly complex animals.

The scientists cited the worm C. elegans, which to date is the only animal for which there is a complete static map, or "connectome." That worm has just 302 neurons with 7,000 connections. The authors propose moving on to the Drosophila fly, which has 135,000 neurons; the zebra-fish, with roughly one million neurons; the mouse; and then the Etruscan shrew, the smallest known mammal, whose cortex is composed of roughly a million neurons.

But the leap to the human brain is so enormous that one of the scientists who has participated in planning sessions, the neuroscientist Terry Sejnowski from the Salk Institute, has called the challenge "the million neuron march."

While the researchers have proposed a wide range of technologies that might be applied to the problems, many of them are still prototypes or speculative. Some of them, like nano-robots being designed at places like the Wyss Institute laboratory at Harvard, seem like they are straight from "Fantastic Voyage," the 1966 movie that imagined the ability to shrink submarines and humans — specifically, Raquel Welch — for journeys through the human body.

Moreover, many technologies now used to sample human brain activity at high resolution require opening the skull, dramatically restricting what is possible. Progress is being made using those available techniques, but only at a basic level.

Still, last week in the journal Nature a group of neurosurgeons at the University of California, San Francisco, reported significant new insights into mechanisms of the language function of the human brain. That research, which was conducted with permission from three people who had severe epileptic seizures, involved installing a dense sensor mesh of electrodes on the surface of their brains. The 264 electrodes each sampled from an area that might encompass as many as millions of neurons, according to Dr. Edward F. Chang, a neurosurgeon who led the team.

Although the sensor's resolution was crude, it was four times more powerful than what has been used until now. It revealed how the speech centers in the human cortex control the larynx, tongue, jaw, lips and face, all of which are involved in making the sounds that constitute human speech.

"I don't think this was a major technological innovation," Dr. Chang said. "But it demonstrates the power of even incremental advances, and shows how they can have a major impact on what we can understand."

The goal of the University of California group is ultimately to gain enough understanding of the speech mechanism in the brain to be able develop sophisticated prosthetics, making it possible for victims of paralysis or stroke to speak.

It is that potential — and more — that has excited scientists, and generated pressure for a multibillion dollar effort to develop a human brain activity map, backed by the United States government, in partnership with research foundations and institutions.

The project's roots lie in a small scientific conference in London in September 2011.

The meeting had been organized by Miyoung Chun, a molecular biologist who is vice president of scientific programs at the Kavli Foundation. Its goal was to gather some of the world's best neuroscientists and nano-scientists and figure out how they might work together, according to Ralph J. Greenspan, a molecular biologist at the University of California, San Diego, who attended the conference.

For two days the scientists mostly "talked at each other," he recalled. Then George M. Church, a Harvard molecular geneticist who helped start the original Human Genome Project in 1984, said, "All right I've heard all of you say what you can do, but I haven't heard anyone say what you really want to do."

"I want to be able to record from every neuron in the brain at the same time," Dr. Yuste replied.

In the next year, two white papers calling for a concerted and heavily funded national effort were published. Kristof Koch and R. Clay Reid, of the Allen Institute of Brain Science in Seattle, proposed mapping the mouse brain completely. And in June, six scientists, including Dr. Yuste, Dr. Church, Dr. Greenspan and Dr. Chun, wrote the Neuron paper.

Last fall when Thomas A. Kalil, the deputy director of the White House Office of Science and Technology Policy, encountered a group of neuroscientists at a conference, the idea of a broad multiagency government project took hold.

The scientists acknowledge that, beyond the scientific hurdles, the Brain Activity Map project faces significant technical challenges.

At a meeting in Pasadena, Calif., on Jan. 17 to explore the data storage needs of the proposed mapping project, computer scientists, neuroscientists and nanoscientists concluded that it would require three petabytes of storage capacity to capture the amount of information generated by just one million neurons in a year.

There are one million gigabytes in a petabyte. The Large Hadron Collider in Geneva generates about 10 petabytes of data annually. If the brain contains between 85 and 100 billion neurons, that means that the complete brain generates about 300,000 petabytes of data each year.

One facet of the project certain to create controversy is that the scientists are also developing technologies that manipulate neurons, raising the specter not just of mind reading, but mind control. The scientists argue that it is in controlling neurons that they can gain valuable information on brain function.

An assistant at Koop's Dartmouth institute, Susan Wills, said he died Monday in Hanover, where he had a home. She didn't disclose his cause of death.

Koop wielded the previously low-profile post of surgeon general as a bully pulpit for seven years during the Ronald Reagan and George H.W. Bush administrations.

An evangelical Christian, he shocked his conservative supporters when he endorsed condoms and sex education to stop the spread of AIDS.

He carried out a crusade to end smoking in the United States — his goal had been to do so by 2000. A former pipe smoker, he said cigarettes were as addictive as heroin and cocaine.

Koop's impact was great, although the surgeon general has no real authority to set government policy. He described himself as "the health conscience of the country."

"My only influence was through moral suasion," Koop said just before leaving office in 1989.

By then, his Amish-style silver beard and white, braided uniform were instantly recognizable.

Out of office, he switched to business suits and bow ties but continued to promote public health causes, from preventing childhood accidents to better training for doctors.

"I will use the written word, the spoken word and whatever I can in the electronic media to deliver health messages to this country as long as people will listen," he promised.

In 1996, he rapped Republican presidential hopeful Bob Dole for suggesting that tobacco is not invariably addictive, saying Dole's comments "either exposed his abysmal lack of knowledge of nicotine addiction or his blind support of the tobacco industry."

Although Koop eventually won wide respect with his blend of old-fashioned values, pragmatism and empathy, his nomination in 1981 met a wall of opposition from women's groups and liberal politicians.

Critics said Reagan selected Koop, a pediatric surgeon from Philadelphia, only because of his conservative views, especially his staunch opposition to abortion.

Foes noted that Koop traveled the country in 1979 and 1980 giving speeches that predicted a progression "from liberalized abortion to infanticide to passive euthanasia to active euthanasia, indeed to the very beginnings of the political climate that led to Auschwitz, Dachau and Belsen."

But Koop, a devout Presbyterian, was confirmed after he told a Senate panel he would not use the surgeon general's post to promote his religious ideology. He kept his word.

In 1986, he issued a frank report on AIDS, urging the use of condoms for "safe sex" and advocating sex education as early as third grade.

He also maneuvered around uncooperative Reagan administration officials in 1988 to send an educational AIDS pamphlet to more than 100 million U.S. households, the largest public health mailing ever done.

Koop personally opposed homosexuality and believed sex should be saved for marriage. But he insisted that Americans, especially young people, must not die because they were deprived of explicit information about how the HIV virus was transmitted.

He became a hero to AIDS activists, who chanted "Koop, Koop" at his appearances but booed other officials.

Koop further angered conservatives by refusing to issue a report requested by the Reagan White House, saying he could not find enough scientific evidence to determine whether abortion has harmful psychological effects on women.

Koop maintained his personal opposition to abortion, however. After he left office, he told medical students it violated their Hippocratic oath. In 2009, he wrote Senate Majority Leader Harry Reid urging that health care legislation include a provision to ensure doctors and medical students would not be forced to perform abortions. The letter briefly set off a security scare because it was hand delivered.

Koop served as chairman of the National Safe Kids Campaign and as an adviser to President Bill Clinton's health care reform plan.

At a congressional hearing in 2007, Koop spoke about political pressure on the surgeon general post. He said Reagan was pressed to fire him every day, but Reagan would not interfere.

Koop, worried that medicine had lost old-fashioned caring and personal relationships between doctors and patients, opened an institute at Dartmouth to teach medical students basic values and ethics.

He also was a part-owner of a short-lived venture, drkoop.com, to provide consumer health care information via the Internet. It made its initial public offering of stock in 1999, but expenses outstripped revenue and it was out of business by the end of 2001.

In July 2001, the company agreed to pay $4.25 million in cash to settle lawsuits filed by investors who claimed drkoop.com made false promises. Company officials did not admit wrongdoing.

Koop was born in New York's borough of Brooklyn, the only son of a Manhattan banker and the nephew of a doctor. He said by age 5 he knew he wanted to be a surgeon and at age 13 he practiced his skills on neighborhood cats.

He attended Dartmouth College, where he received the nickname Chick, short for "chicken Koop." It stuck for life.

He received his medical degree at Cornell Medical College, choosing pediatric surgery because so few surgeons practiced it.

In 1938, Koop married Elizabeth Flanagan, the daughter of a Connecticut doctor. They had four children — Allen, Norman, David and Elizabeth. David, their youngest son, was killed in a mountain-climbing accident when he was 20.

Koop was appointed surgeon-in-chief at Children's Hospital in Philadelphia and he also served as a professor at the University of Pennsylvania School of Medicine.

He pioneered surgery on newborns and successfully separated three sets of conjoined twins. He won national acclaim by reconstructing the chest of a baby born with the heart outside the body.

Although raised as a Baptist, he was drawn to a Presbyterian church near the hospital, where he developed an abiding faith. He began praying at the bedside of his young patients — ignoring the snickers of some of his colleagues.

"It used to be said in World War II that there were no atheists in foxholes," he wrote in 1973. "I have found there are very few atheists among the parents of dying children.

"This is a time when religious faith can see a family through trying circumstances."

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Ring reported from Montpelier, Vt. Cass reported from Washington.