четверг, 15 марта 2012 г.

A look at the 2011 Buick Regal CXL

2011 Buick Regal CXL

BASE PRICE: $26,245.

AS TESTED: $29,785.

TYPE: Front-engine, front-wheel-drive, five-passenger, midsize sedan.

ENGINE: 2.4-liter, double overhead cam, direct-injection, inline, Ecotec four-cylinder.

MILEAGE: 19 mpg (city), 30 mpg (highway).

TOP SPEED: 134 …

Nicole Scherzinger, Evan Lysacek lead 'Dancing'

Gold medal figure skater Evan Lysacek and Pussycat Dolls frontwoman Nicole Scherzinger emerged as early favorites on the new season of "Dancing With the Stars."

Scherzinger earned the highest score during Monday's premiere, 25 points out of 30, for a Viennese waltz that judge Bruno Tonioli called "a performance of sparkling finesse." Lysacek's waltz landed him in second place with 23 points.

Scherzinger and Lysacek are among 11 celebrity contestants vying for the mirrorball trophy on the 10th season of the hit ABC dance show.

Astronaut Buzz Aldrin earned the night's lowest score, collecting 14 points out of 30 for his cha-cha. The …

Wrong Sox

Obamarama . . .

Credit Dem presidential contender Barack Obama with putting onhis thinking cap.

- Translation: While heading into a luncheon at Boston CollegeFriday afternoon Obama was handed a Red Sox cap.

- Quoth Obama: "Oh no. I believe in team loyalty. I'm a ChicagoWhite Sox fan."

Gift 'em . . .

So what did Mayor Daley get from his staff Friday for an early65th birthday present?

- Two things: An Olympic torch that doubles as a gavel for use atCity Council meetings --and a pogo stick to practice jumping up anddown if the city wins the 2016 Olympics.

- Sing 'em: Mayor Daley, whose actual birthday is Tuesday, …

среда, 14 марта 2012 г.

Best Sellers-Audio

Weekly charts for the nation's best-selling recorded music as they appear in next week's issue of Billboard magazine. …

Swiss would save big banks from collapse

Switzerland's government would step in to prevent the collapse of either of its two major banks, UBS AG and Credit Suisse Group, the country's economics minister said Thursday.

Doris Leuthard told Swiss public radio DRS in an interview that hasty reactions and panic in the face of the global financial turmoil could do more harm than good.

But she acknowledged that Switzerland too has contingency plans in place.

"Something that's surely important to us all, that none of us want, is for one of our big banks to get into a serious crisis or even go bankrupt," Leuthard said.

"The Federal Council would definitely prevent …

Car hits girl but drives on

A 16-year-old girl was left needing hospital treatment after shewas knocked over in a hit and run.

Police are appealing for witnesses after the teenage pedestrianwas injured in a road traffic collision on Hurstones Lane, Alton, ataround 5pm on Thursday.

The vehicle, described as a three-door silver Citroen Saxo withsprayed black wheel trims, was seen to turn into the lane at speed.

The girl, who was walking her dog near to the community centre,was struck by the vehicle causing her to roll over the …

FDA Targets 20 Over Unapproved Drugs

WASHINGTON - Manufacturers of unapproved extended-release cough and cold drugs that contain an expectorant called guaifenesin have until Nov. 25 to stop shipping the medicines, health officials said Friday.

The Food and Drug Administration said roughly 20 companies make hundreds of timed-release medicines containing guaifenesin that have never undergone agency review. They are expected to stop making the drugs even earlier, by Aug. 27. The drugs are sold both by prescription and over the counter, and as both single-ingredient and combination products.

Friday's action does not affect products containing guaifenesin in immediate-release form, the FDA said. The agency said …

Taiwan seeks foreign tie-up to help chip industry

Taiwan's government said it wants the island's ailing memory chip industry to choose between America's Micron Technology Inc. and Japan's Elpida Memory Inc. to help the chip makers consolidate and end a string of massive losses.

The island's six makers of DRAM, or dynamic random access memory, chips have suffered from a glut of supply as the global economic slump saps demand for electronics and machinery run with semiconductors.

"We will set up a strategic alliance with one of the two firms," the Economics Ministry said in a statement Thursday. "We don't rule out a merger if that helps us deepen cooperation."

Speaking at a …

Expert panel will explore Soviet `thaw'

A Chicago Sun-Times Forum next month on "The Big Thaw - CommonSecurity and Common Sense" will focus on how profound changes in theSoviet Union are affecting Americans and the world.

Speakers at the daylong meeting May 6 will include journalistNicholas Daniloff, an expert on Soviet affairs, and Randall Forsberg,director of the Institute for Defense and Disarmament Studies.

John Marks, director of Search for Common Ground, and VladimirPechatnov, first secretary of the Soviet Embassy and representativeof the Institute for U.S. and Canadian Studies, will open the forumwith a discussion of reform in the Soviet Union.

"It gives us great satisfaction to present …

Anthony helps Knicks avenge loss to Bobcats

NEW YORK (AP) — Carmelo Anthony shook off a poor shooting night to make the tiebreaking basket with 2:39 remaining and score 22 points, and the New York Knicks avenged an embarrassing loss to the Charlotte Bobcats with a 91-87 victory on Monday night.

Amare Stoudemire also shot poorly but had 25 points and 12 rebounds, while Tyson Chandler finished with 20 …

Jets next up in Indy's perfect march

To be perfect or not to be? The Indianapolis Colts don't consider it much of a dilemma, really.

They certainly aren't going to rest quarterback Peyton Manning for long as he pursues an unprecedented fourth NFL MVP award and the career 50,000-yard passing mark. And on Sunday they host the New York Jets, a team that has shown little ability to keep up offensively.

So Manning could get in his work, lift the Colts to a 15-0 record, knock the Jets out of playoff contention and finish off an unbeaten home schedule before heading to the Buffalo Bills for the regular season finale.

And a share of history.

"You don't want to lose a game. …

Will new school have an old name?: ; Isom Cabell was a fascinating figure from past

Isom Cabell Elementary is one of the names proposed for the newschool on the West Side. The other choices are River View Elementaryand West Side Elementary, with a decision to be announced today.

Much has been written about the naming process, which involvedinformal balloting among parents and students.

But little has surfaced about the fascinating figure from thepast with the unusual first name.

Who was Isom Cabell?

He was born in the late 1860s at the Cabell Farm in Institute.

His father was Simon Cabell, a wealthy white man whose family hadonce owned slaves.

Isom's mother was a black woman, Sally Flagg Cabell.

As a boy, Isom lost his arm in a mowing accident. The armreportedly was buried somewhere in the bottomland at Institute.

Rendered useless on the farm, Isom went off to school.

He excelled at what is now West Virginia State University. Heraised money for tuition by giving vocal lessons.

After graduation, he took a teaching job in Moundsville.

A church-going disciplinarian with a musical bent, Isom startedthe first Sunday school at the state penitentiary.

Cabell spent eight years in Marshall County and moved back to theKanawha Valley.

He served as principal at two schools for black children -Islands Elementary and Washington Grade School - on the West Side.

His 81-year-old grandson, Charles Grigsby, remembers Isom as afairly handsome man with dark brown skin and stern face,

"He was quite a gentle person unless provoked," said Grigsby, whowas interviewed by phone from his home in Johnstown, Pa.

Grigsby knows. He provoked him.

That happened one day in the early 1930s when Grigsby and hissister waltzed into Washington late.

Principal Cabell did not tolerate tardiness and forcefully lethis grandchildren know.

"I know he was good at handling a yardstick because he put it onmy bottom a couple times," Grigsby said.

Isom died in 1933. Grigsby remembers seeing the body covered witha sheet.

Isom had a son, Marsden Cabell, who also was an educator and wenton to become an influential figure in the state during the New Deal.

An active Democrat, Marsden worked as the "state supervisor ofNegro activities" for the National Youth Administration, a New Dealprogram that tried to keep young people out of the unemploymentlines.

The new grade school on the West Side will be constructed on thesite of the old Cabell Junior High.

It's not clear whether that school was named in honor of Marsdenor Isom.

According to "Black Past," a history of African Americans in theKanawha Valley, blacks who worked at the Kelly Axe factory grewtired in the 1930s of sending their children on a streetcar to theEast End for junior high school.

So these "proud and aggressive" parents waged a campaign for aschool in their community, wrote authors James Randall and AnnaGilmer.

In 1939, the parents got their school. It was built on FloridaStreet on a lot large enough to hold the school and a footballfield.

"Black Past" says the school was named for Isom.

But the West Virginia Heritage Encyclopedia says it was named forMarsden.

Isom's granddaughter, Eleanor Easley, 68, said she doesn't havestrong feelings about the name of the new school. It's up to thecommunity to decide, she said.

"It's their choice. It's their neighborhood," said Easley, wholives in Institute near a Cabell family graveyard.

Without knowing it at the time, she followed in Isom's footsteps.She went to West Virginia State, taught voice lessons and became aschool teacher.

"You follow things," she said. "It's genetic. You follow thingswithout knowing why."

CHRIS JACKSON/DAILY MAIL PHOTOS Eleanor Easley, the granddaughterof Isom Cabell, looks through notes about Cabell that hergrandmother took.

Eleanor Easley plays a piano piece by Beethoven in her home inInstitute.

Hairston Helps Oregon Upset Arizona

Malik Hairston tied his career high with 29 points and Oregon shot 56 percent from the field Saturday to beat No. 21 Arizona at home for the second year in a row, 84-74.

The Ducks (10-4, 1-1 Pac-10) led by as many as 19 in the first half and the Wildcats (10-4, 1-1 Pac-10) never got closer than five in the second.

Chase Budinger scored 30, two shy of his career best, for the Wildcats, who were without their leading scorer and point guard Jerryd Bayles for the third straight game because of a sprained right knee.

Hairston, one of the Ducks' four returning starters, was 11-for-17 from the field, 3-of-5 from 3-point range. Overall, Oregon was 10-of-21 on 3s, compared to Arizona's 5-of-21.

Bryce Taylor scored 15 and freshman Kamyron Brown 13 for Oregon. Maarty Leunen added 13 points and 11 rebounds.

Nic Wise scored 16 for Arizona. Jordan Hill, on the bench in foul trouble most of the first half, added 12 points, 10 in the second half.

Arizona sliced the lead to 71-66 after Hill's two free throws with 6 1/2 minutes to play. The team's traded baskets. However, Brown's 3-pointer boosted it to 76-68 with 5:39 to go, then Tajuan Porter's 15-footer put the Ducks up 78-68 3:38 from the finish.

The Ducks used a barrage of 3-pointers in a 20-4 outburst that put Oregon ahead 46-27 on Hairston's shot behind the arc with 3:41 left in the half. With Hill, Arizona's best big man, on the bench, the Wildcats managed one field goal in a 6 1/2-minute span.

Budinger, who scored 19 in the first half, cut it 46-32 with a driving layup, then his three-point play sliced it to 48-35. Oregon played for the last shot, but David Bagga, a seldom-used reserve, knocked the ball loose and Nic Wise's layup at the buzzer sliced the lead to 48-37 at the break.

Arizona used a 9-2 run to make it 58-52 when Hill rebounded his missed dunk and scored with 12:33 to play. The Ducks, though, followed with Leunen's rebound basket, then a layup by Kamyron Brown and the lead was 62-54.

The Ducks shot 60 percent in the first half, including 7-of-12 3-pointers. Hairston had 17 first-half points on 7-for-10 shooting.

For the third straight game, the Wildcats were without freshman point guard Jerryd Bayless. The team's leading scorer at 18.5 points per game, Bayless is sidelined with a sprained right knee.

The Ducks had nearly as many points in the first half as they did in the entire game of their 62-54 loss at Arizona State on Thursday night.

вторник, 13 марта 2012 г.

Street food that feels like home

For foodies, Chicago's tapestry of ethnic restaurants offers a window to our big, complicated world.

But as Cinco de Mayo looms -- a party for some, a chance to crack the history book for others -- I was reminded that for many people, restaurants in Pilsen, Little Village and Rogers Park offer a taste of mom's and grandma's kitchen.

So it was on a recent visit to Edgewater's Huarache Dona Chio, 1547 W. Elmdale, named last year one of LTHForum.com's "Great Neighborhood Restaurants," where a man sitting alone at one of the five tables explained to me what drew him here almost nightly, the namesake huarache but one of those things.

He lives nearby, he said, and the food was a taste of home -- on his way home.

The huarache (pronounced wah-rah-cheh), so named for its resemblance to the Mexican sandal, is an oval-shaped, fried masa base topped with green or red sauce, onions, potato, cilantro and any manner of protein (ground beef, tongue, even sunflower) and finished with queso cheese.

You can find stands and little restaurants serving huaraches all over Mexico City, the husky, bearded gentleman told me.

Indeed, the "Estilo D.F." -- a line on Dona Chio's menu -- means Distrito Federal, a reference to Mexico City as the nation's seat of power.

Mike Baruch, in his book Street Food Chicago, reminds us that we can get a taste of regional Mexican fare at the Maxwell Street Market, which has existed in some form or another since 1912. There, Latino street vendors serve up antojitos, or "little whims."

In the spirit of the open-air market, a half-wall separates the small dining area from the cooks at Dona Chio, offering curious diners a glimpse of how their meal is assembled.

When making huaraches, a cook grabs a handful of masa dough -- made from a family recipe -- from a big plastic tub, flattens and fries it, then dresses it up.

For $6, it's an affordable meal.

Enjoy huaraches at Huarache Dona Chio and across the city, including at Huaraches Restaurant, 3021 W. Lawrence; Frontera Fresco, on the 7th floor of Macy's, 111 N. State, and El Taco Veloz, 1745 W. Chicago.

Color Photo: Lisa Donovan, Sun-Times / The signature offering at Huarache Dona Chio.

The Boulder blues: ; Mountaineers stumble in overtime against Colorado

BOULDER, Colo. - Quinton Andrews emerged from an angry, anguishedlocker room holding a box of Kentucky Fried Chicken, a postgame mealthat's supposed to fill up the players, but must have been uselesson a night that left West Virginia's Mountaineers feeling empty.

On the side of the box was a slogan: Make any gathering great.

This was the exception.

"We feel like the worst team in the world right now," the juniorsafety said calmly behind bloodshot eyes.

No. 25 WVU, which began the season ranked No. 8 and projectedonce again to compete for a national championship, dropped a secondconsecutive game with a 17-14 overtime loss to Colorado (3-0)Thursday. Consecutive defeats for the first time in four years sentthe Mountaineers on another dejected, dubious stroll to their lockerroom as many of the 51,883 in attendance rushed Folsom Field.

Buffaloes kicker Aric Goodman kicked a 25-yard field goal to winthe game only moments after WVU's Pat McAfee hit the left uprightfrom 23 yards out.

"I feel sorry for Pat McAfee," Coach Bill Stewart said. "I don'tknow what happened, if it was the snap, the hold or the kick, but hemissed it. He's made a bunch for us, but he missed that one and Ihate that for him. I really do."

McAfee did not lose the game, though, and offensive coordinatorJeff Mullen was quick to highlight the problem that again plaguedthe Mountaineers.

"The story of the game was all those third-and-shorts," he said."We just didn't get them."

WVU (1-2) finished 3-for-13 on third down and failed in criticalspots when the need for a true blocking fullback was apparent.

"Third downs?" Stewart said when asked for a solution to aproblem that's seen his team go 12 for 34 in three games. "We've gotto make third downs."

Trailing 14-7 in the third quarter, the offense moved to theColorado 19-yard line, but White came up inches short of the firstdown on third-and-2. Stewart decided not to go for a field goal andWhite tried to sneak for the first down, but was stopped.

Colorado punted and White tied the game on a 39-yard run on whichhe dropped back and pump-faked before dashing through the middle.

The defense, which held Colorado scoreless the final 55:10 ofregulation and stopped nine of the final 11 third downs, forced apunt late in the fourth quarter and the Mountaineers had the ball attheir own 20 with 2:09 remaining.

They were at the Colorado 47 with a third-and-1 with 24 secondsto play. Noel Devine lost a yard and the Mountaineers sent the gameto overtime.

Once there, they came up short again. On third-and-1 at theColorado 11, White angrily called a timeout and barked at someonewho was out of position.

"We had a misalignment and Pat saw it and burned the timeout sowe could get it correct," Mullen said.

The Mountaineers returned with tight end Tyler Urban lined upnext to the right tackle, reserve offensive lineman Don Barclaylined up next to the left tackle and Will Johnson at fullback infront of Jock Sanders in an I-formation. Urban motioned left andSanders followed Johnson as he attempted to go off tackle to theleft side.

"We talked about that play-call earlier game and said the nextthird-and-short, we've got to use it," Mullen said. "That's our bestplay there."

Sanders lost a yard.

"I like to get the back's shoulders downhill when you need incheslike that rather than get them going laterally," Mullen said. "Whenwe have short yardage situations, you want to get your linemen toplay forward and your tailback to play forward."

White carried 19 times for 148 yards and scored twice. Devinegained 133 yards on a career-high 26 carries. No opponent had runfor more than 100 yards at Folsom Field since 2004.

The Mountaineers finished with 311 yards on the ground, butpassed for only 43. White was 10-for-14 and Brad Starks was 0-for-1as he came up short on a double-pass to a wide-open Sanders in thefourth quarter.

"We might have scored, maybe could have done some good things,"Stewart said. "But maybes don't get it done. Getting it done gets itdone."

The near-misses loomed as large as they did because the defenseplayed better as the game progressed.

"There were times we looked like a dominant defense," saidAndrews, who had a game-high 15 tackles.

After giving two touchdowns to start the game - one long drive,one short drive after a turnover - the defense allowed almostnothing. It forced two turnovers, pressured quarterback CodyHawkins, made sure tackles and improved immensely on third down.

The Buffaloes punted on their five second-half possessions.

"My hat's off to Coach (Jeff) Casteel," Mullen said. "His defensegave a winning performance. I feel sick to my stomach we didn't dowhat we had to do to get enough points on the board."

Hawkins and receiver Josh Smith picked the secondary apart on thefirst drive, which ended with Smith catching an easy 38-yardtouchdown from Hawkins as defenders chased. Hawkins was 6-for-8 for76 yards on the drive and Smith caught four passes for 70 yards andconverted two third downs with receptions.

The Mountaineers gave it back three plays later when Whitecompleted a short screen to Starks, who danced around as the defensepounced. Brandon Nicolas came all the way over from nose guard toforce the fumble. Defensive end Maurice Lucas recovered at the WVU28 and Colorado took a 14-0 lead with a 13-yard pass from Hawkins toPatrick Devenny - on third down.

Colorado hadn't scored in the first quarter in its first twogames.

White's 44-yard run down the left sideline gave WVU the ball atColorado's 9-yard line and he scored three plays later on a 5-yarddraw.

The teams combined for 240 yards of total offense in the firstquarter. White ran for 67 yards and Hawkins was 10-for-14 for 105yards. He finished 22-for-33 for 179 yards.

Colorado 17, West Virginia 14 (OT)

West Virginia 7 0 7 0 0 -14

Colorado 14 0 0 0 3 -17

First Quarter

Col-Jo.Smith 38 pass from C.Hawkins (Goodman kick), 12:14.

Col-Devenny 13 pass from C.Hawkins (Goodman kick), 10:10.

WVU-P.White 6 run (McAfee kick), 7:33.

Third Quarter

WVU-P.White 39 run (McAfee kick), 4:49.

Overtime

Col-FG Goodman 25.

A-51,883.

WVU Col

First downs 16 24

Rushes-yards 52-311 45-187

Passing 43 179

Comp-Att-Int 10-15-0 22-33-1

Return Yards 75 15

Punts-Avg. 7-44.3 7-47.6

Fumbles-Lost 1-1 2-1

Penalties-Yards 7-91 7-55

Time of Possession 29:21 30:39

INDIVIDUAL STATISTICS

RUSHING-West Virginia, P.White 19-148, Devine 26-133, Sanders 7-30. Colorado, Stewart 28-166, Scott 10-35, Crawford 1-2, Sumler 1-2, Team 1-0, Jo.Smith 1-(minus 6), C.Hawkins 3-(minus 12).

PASSING-West Virginia, P.White 10-14-0-43, Starks 0-1-0-0.Colorado, C.Hawkins 22-33-1-179.

RECEIVING-West Virginia, Devine 3-11, Jalloh 2-20, Gonzales 1-11, Arnett 1-5, Johnson 1-3, Sanders 1-0, Starks 1-(minus 7).Colorado, Jo.Smith 5-75, McKnight 4-21, Devenny 3-26, Stewart 3-16,Crawford 2-23, Scott 1-15, Cantrell 1-4, J.Behrens 1-1, Williams 1-1, Sumler 1-(minus 3).

(Mennonite Central Committee)

Abbotsford, B.C.--A Mennonite Central Committee training program won recognition at the recent Fraser Valley Cultural Diversity awards. "Above the Underground" is training in retail and customer service. Participants receive training in a clothing store, as well as help with resume writing, job search and computers. In six years, the program has had nearly 250 participants, 90 percent of whom were women and more than 75 percent visible minorities. The program, under MCC B.C.'s Employment Development, is funded by the provincial government. The program competed against Walmart, Envision Financial and Revy for the award.--From MCC B.C. release

The Dependence of All-Atom Statistical Potentials on Structural Training Database

ABSTRACT

An accurate statistical energy function that is suitable for the prediction of protein structures of all classes should be independent of the structural database used for energy extraction. Here, two high-resolution, low-sequence-identity structural databases of 333 [alpha]-proteins and 271 [beta]-proteins were built for examining the database dependence of three all-atom statistical energy functions. They are RAPDF (residue-specific all-atom conditional probability discriminatory function), atomic KBP (atomic knowledge-based potential), and DFIRE (statistical potential based on distance-scaled finite ideal-gas reference state). These energy functions differ in the reference states used for energy derivation. The energy functions extracted from the different structural databases are used to select native structures from multiple decoys of 64 [alpha]-proteins and 28 [beta]-proteins. The performance in native structure selections indicates that the DFIRE-based energy function is mostly independent of the structural database whereas RAPDF and KBP have a significant dependence. The construction of two additional structural databases of [alpha]/[beta] and [alpha] + [beta]-proteins further confirmed the weak dependence of DFIRE on the structural databases of various structural classes. The possible source for the difference between the three all-atom statistical energy functions is that the physical reference state of ideal gas used in the DFIRE-based energy function is least dependent on the structural database.

INTRODUCTION

One simple method for estimating the interaction between the proteins and within a single protein is the knowledge-based approach in which known protein structures are used to generate the statistical potentials (or energy functions; Tanaka and Scheraga, 1976). Knowledge-based statistical potentials have been applied to fold recognition and assessment (Bryant and Lawrence, 1993; Casari and Sippl, 1992; Hendlich et al., 1990; Jones et al., 1992; Lu and Skolnick, 2001; Melo et al., 2002; Miyazawa and Jernigan, 1999; Samudrala and Moult, 1998; Sippl, 1990; Zhou and Zhou, 2004), structure predictions (Lee et al., 1999; Pillardy et al., 2001; Simons et al., 1997; Skolnick et al., 1997; Sun, 1993; Tobi and Elber, 2000; Vendruscolo et al., 2000), and validations (Luthy et al., 1992; MacArthur et al., 1994; Melo and Feytmans, 1998; Rojnuckarin and Subramaniam, 1999; Sippl, 1993), docking and binding (Altuvia et al., 1995; Liu et al., 2004; Pellegrini and Doniach, 1993; Wallqvist et al., 1995; Zhang et al., 1997), and mutation-induced changes in stability (Gilis and Rooman, 1996, 1997; Zhang et al., 1997; Zhou and Zhou, 2002).

One natural consequence of this commonly used statistical approach is that the outcome (the energy function) is strongly dependent on input (the structural database). For example, the structural database of single-chain proteins and the interface database of dimeric proteins produce quantitatively different pair potentials for folding and binding studies (Lu et al., 2003; Moont et al., 1999). This is caused by significantly different compositions of amino acid residues at the surface, core, and interface of proteins (Glaser et al., 2001; Lu et al., 2003; Ofran and Rost, 2003). In another example, the residue-level, distance-dependent, Sippl potential extracted from all-[alpha] protein structures is quantitatively different from that extracted from all-[beta] protein structures (Furuichi and Koehl, 1998). This suggests that different structural patterns (topology) also change the outcome of the statistical energy function. The distance-independent statistical energy parameters, however, appear to be less sensitive to different subsets of protein structure database except that there is large difference between the parameters from the crystallographic structures and that from the NMR structures (Godzik et al., 1995).

The database dependence of statistical energy functions, however, is unphysical. This is because the same physical interaction (water-mediated interaction between amino-acid residues) is responsible for protein folding and binding and for the formation of [beta]-strands and [alpha]-helices. The unphysical, database dependence of a statistical potential is difficult to avoid because it is equivalent to requiring the output to be independent of (or insensitive to) different input information.

Recently, a residue-specific all-atom, distance-dependent potential of mean-force was extracted from the structures of single-chain proteins by using a physical state of uniformly distributed points in finite spheres (distance-scaled, finite, ideal-gas reference, i.e., DFIRE, state) as the zero-interaction reference state (Zhou and Zhou, 2002). Remarkably, the physical reference state yields a potential of mean-force that no longer possesses some unphysical characteristics associated with other statistical potentials. It was shown that the accuracy of DFIRE-based potential is insensitive to the partitioning of hydrophobic and hydrophilic residues within a protein (Zhou and Zhou, 2002). More importantly, the new structure-derived potential can quantitatively reproduce the likelihood of a residue to be buried (i.e., the composition difference of amino-acid residues between core and surface; Zhou and Zhou, 2003). The potential also yields a stability scale of amino acid residues in quantitative agreement with that independently extracted from mutation experimental data (Zhou and Zhou, 2003). Moreover, the monomer potential (derived from single-chain proteins) is found to be equally successful in discriminating against docking decoys, distinguishing true dimeric interface from crystal interfaces, and predicting binding free energy of protein-protein and protein-peptide complexes (Liu et al., 2004). The independence of the performance for the systems with various amino-acid compositions suggests that the DFIRE-based potential possesses some physical characteristics not observed in some other knowledge-based potentials.

The above results raise an interesting question: does the DFIRE-based potential depend on the structural database used for statistics? Although the performance of the DFIRE potential on structure selections has been shown to be insensitive to the size of the database (number of protein structures; Zhou and Zhou, 2002) and the database of either single-chain or dimeric proteins (Liu et al., 2004), it is not clear whether or not the structural database of all-[alpha] proteins will yield a DFIRE potential that is different from that generated from the database of all-[beta] proteins. Answering this question is important for the application of the DFIRE-based statistical energy function to structure prediction of proteins with different structural topology.

In this article, we built structural databases of all-[alpha], all-[beta], [alpha] + [beta], and [alpha]/[beta] proteins based on SCOP classification. The database dependence of three all-atom knowledge-based potentials (i.e., RAPDF, Samudrala and Moult, 1998; atomic KBP, Lu and Skolnick, 2001; and DFIRE, Zhou and Zhou, 2002) are compared. Results show that unlike RAPDF and KBP, the DFIRE energy function is mostly independent of the database used for training. The origin for the difference in database dependence between DFIRE and RAPDF/KBP is discussed.

METHODS

Composition-averaged observed state as the reference state

Distance-scale finite ideal-gas reference (DFIRE) state

Structural training databases

To test the dependence of three statistical potentials (RAPDF, atomic KBP, and DFIRE) on training databases, we built training databases of all-[alpha] and all-[beta] proteins based on the SCOP classification (1.63 release; Conte et al., 2002; Murzin et al., 1995). Specifically, we began with the <40% identity set built by the authors of SCOP (http://astral.stanford.edu/), then removed the structures obtained by the NMR methods, the structures whose resolution >2.5 [Angstrom], the structures from composite domains (Furuichi and Koehl, 1998; Zhang and Kim, 2000), and the structures not from all-[alpha] or all-[beta] structure classes (defined by authors of SCOP). Then, we extracted the experimentally determined secondary structural states ([alpha], [beta], and others) of residues in these structures from DSSP database (Kabsch and Sander, 1983) using a simple mapping scheme similar to Zhang and Kim (2000). We removed the structures in [alpha] ([beta]) class that have >10% content of [beta] ([alpha]). Finally, we removed the structures with >30% identity to decoys (calculated with FASTA package; Pearson, 1990; Pearson and Lipman, 1988). The final [alpha]-protein and [beta]-protein databases have 333 and 271 single-domain proteins, respectively.

In addition, we built training databases of [alpha]/[beta] and [alpha]+[beta] proteins. The procedure used to build them is exactly the same as described above except that the [alpha]/[beta] and [alpha]+[beta] classes (according to SCOP definition) of <40% identity SCOP set are used instead. We required that both [alpha]/[beta] and [alpha]+[beta] proteins have > 10% content of [alpha] and [beta]. There are 515 [alpha]/[beta] and 399 [alpha]+[beta] single-domain proteins that are <30% identity to decoys. (A list of proteins is given in http://theory.med.buffalo.edu.) The DFIRE energy functions based on 333 [alpha]-proteins, 271 [beta]-proteins, 515 [alpha]/[beta], and 399 [alpha]+[beta] proteins are labeled as DFIRE-[alpha], DFIRE-[beta], DFIRE-[alpha]/[beta], and DFIRE-[alpha]+[beta], respectively. The original structural database (Zhou and Zhou, 2002) for calculating N^sub obs^(i, j, r) was a structural database of 1011 non-homologous (<30% homology) proteins with resolution <2 [Angstrom], which was collected by Hobohm et al. (1992) (http://chaos.fccc.edu/research/labs/dunbrack/culledpdb.html). The DFIRE energy function extracted from this database will be labeled as DFIRE-all.

In addition to generating several DFIRE energy functions by using the new structural databases, RAPDF and atomic KBP potentials are also regenerated for comparison. The bin procedures for RAPDF and KBP are as follows. For RAPDF (Samudrala and Moult, 1998), the first bin covers 03.0 [Angstrom] and the distance between 3.0 [Angstrom] and 20 [Angstrom] is binned every 1 [Angstrom]. The total number of bins is 18. All 18 bins with a cutoff distance of 20 [Angstrom] are used for scoring. For atomic KBP (Lu and Skolnick, 2001), the distance between 1.5 [Angstrom] and 14.5 [Angstrom] is binned every 1 [Angstrom] and the last bin is from 14.5 [Angstrom] to infinite. The total number of bins is 14. The first- and second-sequence neighbors are excluded whereas backbone atoms are included in counting contacts. When used in scoring, only the bins covering 3.5-6.5 [Angstrom] are used. In all cases, contacts between atoms within a single residue are excluded from the counts and scoring. In case of zero pairs, both potentials are set to be 2[eta] kcal/mol. No attempts were made to optimize these parameters and/or procedures presented by the original articles for possibly better performance. There are RAPDF-[alpha], RAPDF-[beta], KBP-[alpha], and KBP-[beta], depending on the structural database used.

Multiple decoy sets for [alpha]- and [beta]-proteins

The database dependence of the energy functions was tested by the performance on structural discrimination. We established the decoy sets for all-[alpha] and all-[beta] proteins from the 4state_reduced set (Park and Levitt, 1996), lmds set (through conformational enumeration of loop region, Keasar and Levitt, 2003), fisa set (Simons et al., 1997), fisa_casp3 set (Simons et al., 1997), Rosetta (through Rosetta method; Simons et al., 1997), lattice_ssfit (through conformational enumeration on whole protein, Samudrala et al., 1999), hg_structural (through comparative modeling), LKF (through minimizing the number of violations of van der Waals constraints, Loose et al., 2004), and CASP4 decoy sets (generated by numerous protein structure prediction teams using a variety of methods, Feig and Brooks, 2002). There are 64 and 28 decoy sets for [alpha] (with [beta]-content <10%) and [beta] (with [alpha]-content <10%) proteins, respectively. All these 92 proteins have <30% identity to the proteins in the training databases of all-[alpha], all-[beta], [alpha]+[beta], and [alpha]/[beta] proteins. The complete list of these proteins is shown in Table 1.

Structure selections from decoys

RESULTS AND DISCUSSION

We focus first on the energy functions extracted from the databases of the all-[alpha] structures and all-[beta] structures. Because the structural difference between all-[alpha] and all-[beta] structures is the largest among all structural classes, the database dependence is likely the largest between the energy functions extracted from these two databases. It is known that [alpha]-proteins involve mostly local contacts (contacts between the residues with short sequence separations) whereas [beta]-proteins involve mostly nonlocal contacts.

Fig. 1 compares the performance of energy functions obtained from the databases of the all-[alpha] structures and all-[beta] structures on structural discrimination of all-[alpha] proteins and all-[beta] proteins. The performance is characterized by the success rate in ranking native structures within a given number of energy-ranked structures (top-ranked structures, N^sub t^). For all three methods (RAPDF, KBP, and DFIRE), there is some degree of database dependence because an [alpha]-protein-trained energy function gives a higher success rate in structure selections of [alpha]-proteins than a [beta]-proteintrained energy function. Similarly, a [beta]-protein-trained energy function gives a higher success rate in structure selections of [beta]-proteins than an [alpha]-protein-trained energy function. However, DFIRE has a substantially smaller dependence than either RAPDF or KBP. For example, for the top 10 ranking (N^sub t^ = 10), the difference between the success rates of selecting [alpha]-proteins given by an energy function trained by the two structural databases is 6% for RAPDF and 14% for KBP, but only 2% for DFIRE. For the structure selection of [beta]-proteins, the corresponding difference is 17% for RAPDF, 18% for KBP, and 0% for DFIRE. Fig. 1 shows that at every number of top-ranked structures, DFIRE consistently gives the smallest difference between the two success rates among RAPDF, KBP, and DFIRE.

The difference between the energy functions trained by different structural databases can also be visualized by comparing the total energies of the native structures of 64 [alpha]-proteins and 28 [beta]-proteins given by the energy functions. Fig. 2 compares the energy given by the [alpha]-protein-trained potentials with that given by the [beta]-protein-trained potentials. The root mean-squared deviations between the two energy values for the 64 [alpha]-proteins are 0.296 for RAPDF, 1.07 for KBP, and 0.132 for DFIRE, respectively. (The relative difference is used, i.e., the energy difference is divided by the average energy predicted by two energy functions.) The corresponding root mean-squared deviation values for the 28 [beta]-proteins are 0.342 for RAPDF, 0.694 for KBP, and 0.068 for DFIRE, respectively. Thus, the DFIRE gives the smallest database dependence in native energy. In fact, both RAPDF and KBP show a systematic deviation. An [alpha]-protein-trained energy function always gives a lower energy to [alpha]-proteins than a [beta]-protein-trained energy function does. Similarly, a [beta]-protein-trained energy function always gives a lower energy to [beta]-proteins than an [alpha]-protein-trained energy function does. The lower the energy, the stronger the systematic deviation. In contrast, the correlation slope between the energy given by the [alpha]-protein-trained DFIRE potential and that given by the [beta]-protein-trained DFIRE potential is very close to 1 for either [alpha]-proteins or [beta]-proteins.

To further illustrate the database dependence, the Z-scores given by energy functions trained by different databases are shown in Fig. 3. It is clear that DFIRE has the smallest database dependence on Z-scores. For [alpha]-protein decoys, the root mean-square deviation values of Z-scores between two database-trained energy functions are 1.95 for RAPDF, 1.07 for KBP, and 0.387 for DFIRE, respectively. The corresponding values for [beta]-protein decoys are 0.767 for RAPDF, 0.457 for KBP, and 0.257 for DFIRE, respectively.

For [alpha]-proteins, there is one significant outlier for DFIRE at high Z-score value where the Z-score given by DFIRE-[beta] is lower than that given by DFIRE-[alpha]. This is contributed by 1beo in the lattice_ssfit decoy set. We found that the energy differences given by DFIRE-[alpha] and DFIRE-[beta] are in fact quite small for both decoys and native states (<10%). The large difference in Z-score resulted from an artificially narrow range of DFIRE energies of decoys relative to the energy difference between native state and decoys.

Thus, the ranks of native state energies (or success rates), the energies of native states, and Z-scores predicted by the energy functions extracted from all-[alpha] and all-[beta] structures all indicate that DFIRE has a significantly smaller database dependence than either RAPDF or KBP. In addition to the databases of all-[alpha] and all-[beta] structures, we also built the database of [alpha]+[beta] and [alpha]/[beta] structures. Because [alpha]+[beta] and [alpha]/[beta] structures contain the structural features of both [alpha]-helices and [beta]-strands, one expects that the results based on the energy functions extracted from mixed [alpha]- and [beta]-structural elements are closer to the results extracted from the structures of all proteins. Indeed, as Fig. 4 shows, the success rates predicted by the DFIRE potential extracted from the original database (1011 proteins, DFIRE-all; Zhou and Zhou, 2002) are closer to those by the potential extracted from [alpha]+[beta] and [alpha]/[beta] structures than those by the potentials from [alpha]- and [beta]-databases. For example, at the top-10 ranking, the differences between the average success rates over rankings 1-10 are 2.4% between DFIRE-all and DFIRE-[alpha], 2.4% between DFIRE-all and DFIRE-[beta], 1.1% between DFIRE-all and DFIRE-[alpha]+[beta], and 0.2% between DFIRE-all and DFIRE-[alpha]/[beta]. The difference between the success rate given by DFIRE-all and that by DFIRE-[alpha]/[beta] is the smallest. This is somewhat expected because the [alpha]/[beta] structural class contains mixed elements of [alpha]-helices and [beta]-strands whereas [alpha]+[beta] structures do not mix these two structural elements. The database for all proteins should be more similar to a random mixture of [alpha]- and [beta]-structural elements. The database independence of DFIRE potential further confirms the previous finding that the performance of DFIRE potential in structure selection is insensitive to the number of proteins used in the database (200 or more) and whether or not the target proteins are contained in training structural databases (Zhou and Zhou, 2002). It should be emphasized that the DFIRE potential is not only mostly database independent but also has higher success rates than RAPDF and KBP in either [alpha]-protein decoys or [beta]-protein decoys.

Fig. 5 provides two examples of the pair potentials given by RAPDF, KBP, and DFIRE methods using three different structural databases. One is the potential between C^sub [beta]^ atoms of Leu and Asp and the other is between backbone N atom of Val and O atom of Trp. It is difficult, however, to judge the difference between the potentials extracted from different structural databases from the individual pair potential.

To further understand the source for the difference between the three methods, one can compare the reduced reference states [N^sub exp^(r) = [summation operator]^sub ij^N^sub exp^(i,j,r)] given by the methods. For both RAPDF and KBP, N^sub exp^(r) = [summation operator]^sub ij^N^sub exp^(i,j,r) = N^sub obs^(r). For DFIRE, N^sub exp^(r) = (r/ r^sub cut^)^sup [alpha]^([Delta]r/[Delta]r^sub cut^)N^sub obs^(r^sub cut^). Thus, the database dependence of the reduced reference state in the DFIRE only comes from N^sub obs^(r) at r = r^sub cut^, whereas it is N^sub obs^(r) at all distance for RAPDF and KBP. Fig. 6 plots the ratio of N^sub exp^(r) obtained from the [alpha]-protein database or the [beta]-protein database to that from the 1011-protein database. Even though all reference states have the database dependence, the database dependencies of RAPDF and KBP are significantly larger than that of DFIRE. It should be noted that the database dependence of N^sub obs^(r^sub cut^) is normal because the number of pairs at a certain distance is strongly dependent on the number of proteins. This dependence is apparently canceled by the database dependence of N^sub obs^(i, j, r) in DFIRE. We emphasize that the distance dependence of the reduced reference state [N^sub exp^(r)] is the same for RAPDF and KBP, but, the dependence of N^sub exp^(i, j, r) on atomic types for RAPDF and KBP is different (see Eqs. 2 and 3).

CONCLUDING REMARKS

The examination of the database dependence of statistical energy functions is important for an accurate prediction of protein structures. An accurate energy function should be capable of folding proteins with [alpha], [beta], or any other structural topologies. This requires the statistical energy function to be independent of the structural database used for energy extraction. Here, the database dependences of RAPDF, atomic KBP, and DFIRE are examined based on their performance on structure selections. It is shown that the DFIRE potential is the least dependent on the structural database used for energy derivation, compared to RAPDF and atomic KBP. The significant database dependence of all-atom KBP/RAPDF statistical potentials confirms the previous finding for the database dependence of the residue-level Sippl potential with smaller databases of different structural classes (Furuichi and Koehl, 1998). The origin of significant database dependence for RAPDF and atomic KBP is likely due to significant database dependence of their reference states. This highlights the importance of choosing an appropriate reference state for deriving statistical energy function. The mostly independent DFIRE energy function on the structural database, together with the independence of its performance for the systems with various amino-acid compositions (surface vs. core, monomer vs. dimeric interface; Zhou and Zhou, 2002, 2003; Liu et al., 2004), indicates that a physical reference state produces not only a physically but also a quantitatively more accurate statistical energy function.

We thank Professor Charles L. Brooks and Professor Michael Feig for the CASP4 decoy sets.

This work is supported by the National Institutes of Health (R01 GM 966049 and R01 GM 068530); a grant from the Howard Hughes Medical Institute to the State University of New York, Buffalo; and by the Center for Computational Research and the Keck Center for Computational Biology at the State University of New York, Buffalo.

[Reference]

REFERENCES

Altuvia, Y., O. Schueler, and H. Margalit. 1995. Ranking potential binding peptides to MHC molecules by a computational threading approach. J. Mol. Biol. 249:244-250.

Bryant, S. H., and C. E. Lawrence. 1993. An empirical energy function for threading protein sequence through the folding motif. Proteins. 16:92-112.

Casari, G., and M. J. Sippl. 1992. Structure-derived hydrophobic potential. Hydrophobic potential derived from x-ray structures of globular proteins is able to identify native folds. J. Mol. Biol. 224:725-732.

Conte, L. L., S. E. Brenner, T. J. P. Hubbard, C. Chothia, and A. Murzin. 2002. SCOP database in 2002: refinements accommodate structural genomics. Nucl. Acid Res. 30:264-267.

Feig, M., and C. L. Brooks III. 2002. Evaluating CASP4 predictions with physical energy functions. Proteins. 49:232-245.

Friedman, H. L. 1985. A Course in Statistical Mechanics. Prentice-Hall, Englewood Cliffs, New Jersey.

Furuichi, E., and P. Koehl. 1998. Influence of protein structure databases on the predictive power of statistical pair potentials. Proteins. 31:139-149.

Gilis, D., and M. Rooman. 1996. Stability changes upon mutation of solvent-accessible residues in proteins evaluated by database-derived potentials. J. Mol. Biol. 257:1112-1126.

Gilis, D., and M. Rooman. 1997. Predicting protein stability changes upon mutation using database-derived potentials: solvent accessibility determines the importance of local versus non-local interactions along the sequence. J. Mol. Biol. 272:276-290.

Glaser, F., D. Sternberg, I. Vasker, and N. Ben-Tal. 2001. Residue frequencies and pairing preferences at protein-protein interfaces. Proteins. 43:89-102.

Godzik, A., A. Kolinski, and J. Skolnick. 1995. Are proteins ideal mixtures of amino acids? Analysis of energy parameter sets. Protein Sci. 4:2107-2117.

Hendlich, M., P. Lackner, S. Weitckus, H. Floeckner, R. Froschauer, K. Gottsbacher, G. Casari, and M. J. Sippl. 1990. Identification of native protein folds amongst a large number of incorrect models. The calculation of low energy conformations from potentials of mean force. J. Mol. Biol. 216:167-180.

Hobohm, U., M. Scharf, R. Schneider, and C. Sander. 1992. Selection of representative protein data sets. Protein Sci. 1:409-417.

Jernigan, R. L., and I. Bahar. 1996. Structure-derived potentials and protein simulations. Curr. Opin. Struct. Biol. 6:195-209.

Jones, D. T., W. R. Taylor, and J. M. Thornton. 1992. A new approach to protein fold recognition. Nature. 358:86-89.

Kabsch, W., and C. Sander. 1983. Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers. 22:2577-2637.

Keasar, C., and M. Levitt. 2003. A novel approach to decoy set generation: designing a physical energy function having local minima with native structure characteristics. J. Mol. Biol. 329:159-174.

Lee, J., A. Liwo, and H. A. Scheraga. 1999. Energy-based de novo protein folding by conformational space annealing and an off-lattice united-residue force field: application to the 10-55 fragment of staphylococcal protein A and to apo calbindin D9K. Proc. Natl. Acad. Sci. USA. 96:2025-2030.

Liu, S., C. Zhang, H. Zhou, and Y. Zhou. 2004. A physical reference state unifies the structure-derived potential of mean force for protein folding and binding. Proteins. In press.

Loose, C., J. Klepeis, and C. Floudas. 2004. A new pairwise folding potential based on improved decoy generation and side chain packing. Proteins. 54:303-314.

Lu, H., L. Lu, and J. Skolnick. 2003. Development of unified statistical potentials describing protein-protein interactions. Biophys. J. 84:1895-1901.

Lu, H., and J. Skolnick. 2001. A distance-dependent atomic knowledge-based potential for improved protein structure selection. Proteins. 44:223-232.

Luthy, R., J. U. Bowie, and D. Eisenberg. 1992. Assessment of protein models with three-dimensional profiles. Nature. 356:83-85.

MacArthur, M. W., R. A. Laskowski, and J. M. Thornton. 1994. Knowledge-based validation of protein structure coordinates derived by x-ray crystallography and NMR spectroscopy. Curr. Opin. Struct. Biol. 4:731-737.

Melo, F., and E. Feytmans. 1998. Assessing protein structures with a non-local atomic interaction energy. J. Mol. Biol. 277:1141-1152.

Melo, F., R. Sanchez, and A. Sali. 2002. Statistical potentials for fold assessment. Protein Sci. 430:430-448.

Mitchell, J. B. O., R. A. Laskowski, A. Alex, and J. M. Thornton. 1999. BLEEP-potential of mean force describing protein-ligand interactions. I. Generating potential. J. Comp. Chem. 20:1165-1176.

Miyazawa, S., and R. L. Jernigan. 1999. An empirical energy potential with a reference state for protein fold and sequence recognition. Proteins. 36:357-369.

Moont, G., H. Gabb, and M. Sternberg. 1999. Use of pair potentials across protein interfaces in screening predicted docked complexes. Proteins. 35:364-373.

Moult, J. 1997. Comparison of database potentials and molecular mechanics force fields. Curr. Opin. Struct. Biol. 7:194-199.

Murzin, A. G., S. E. Brenner, T. Hubbard, and C. Chothia. 1995. SCOP: a structural classification of proteins database for the investigation of sequences and structures. J. Mol. Biol. 247:536-540.

Ofran, Y., and B. Rost. 2003. Analyzing six types of protein-protein complexes. J. Mol. Biol. 325:377-387.

Park, B., and M. Levitt. 1996. Energy functions that discriminate x-ray and near-native folds from well-constructed decoys. J. Mol. Biol. 258:367-392.

Pearson, W. R. 1990. Rapid and sensitive sequence comparison with FASTP and FASTA. Methods Enzymol. 183:63-98.

Pearson, W. R., and D. J. Lipman. 1988. Improved tools for biological sequence comparison. Proc. Natl. Acad. Sci. USA. 85:2444-2448.

Pellegrini, M., and S. Doniach. 1993. Computer simulation of antibody binding specificity. Proteins. 15:436-444.

Pillardy, J., C. Czaplewski, A. Liwo, J. Lee, D. R. Ripoll, R. Kamierkiewicz, S. Oldziej, W. J. Wedemeyer, K. D. Gibson, Y. A. Arnautova, J. Saunders, Y.-J. Ye, and H. A. Scheraga. 2001. Recent improvements in prediction of protein structure by global optimization of a potential energy function. Proc. Natl. Acad. Sci. USA. 98:2329-2333.

Rojnuckarin, A., and S. Subramaniam. 1999. Knowledge-based interaction potentials for proteins. Proteins. 36:54-67.

Samudrala, R., and J. Moult. 1998. An all-atom distance-dependent conditional probability discriminatory function for protein structure prediction. J. Mol. Biol. 275:895-916.

Samudrala, R., Y. Xia, M. Levitt, and E. Huang. 1999. A combined approach for ab initio construction of low resolution protein tertiary structures from sequence. Pac. Symp. Biocomput. 4:505-506.

Simons, K. T., R. Bonneau, I. Ruczinski, and D. Baker. 1999. Ab initio protein structure prediction of CASP III targets using ROSETTA. Proteins. 37:171-176.

Simons, K. T., C. Kooperberg, E. Huang, and D. Baker. 1997. Assembly of protein tertiary structures from fragments with similar local sequences using simulated annealing and Bayesian scoring functions. J. Mol. Biol. 268:209-225.

Sippl, M. J. 1990. Calculation of conformational ensembles from potentials of mean force. An approach to the knowledge-based prediction of local structures in globular proteins. J. Mol. Biol. 213:859-883.

Sippl, M. J. 1993. Recognition of errors in three-dimensional structures of proteins. Proteins. 17:355-362.

Skolnick, J., A. Kolinski, and A. R. Ortiz. 1997. MONSSTER: a method for folding globular proteins with a small number of distance restraints. J. Mol. Biol. 265:217-241.

Sun, S. 1993. Reduced representation model of protein structure prediction: statistical potential and genetic algorithms. Protein Sci. 2:762-785.

Tanaka, S., and H. A. Scheraga. 1976. Medium- and long-range interaction parameters between amino acids for predicting three-dimensional structures of proteins. Macromolecules. 9:945-950.

Tobi, D., and R. Elber. 2000. Distance-dependent, pair potential for protein folding: results from linear optimization. Proteins. 41:40-46.

Vendruscolo, M., L. A. Mirny, E. I. Shakhnovich, and E. Domany. 2000. Comparison of two optimization methods to derive energy parameters for protein folding: perception and Z-score. Proteins. 41:192-201.

Vijayakumar, M., and H.-X. Zhou. 2000. Prediction of residue-residue pair frequencies in proteins. J. Phys. Chem. B. 104:9755-9764.

Wallqvist, A., R. L. Jernigan, and D. G. Covell. 1995. A preference-based free energy parameterization of enzyme-inhibitor binding. Applications to HIV-1-protease inhibitor design. Protein Sci. 4:1881-1903.

Xia, Y., E. S. Huang, M. Levitt, and R. Samudrala. 2000. Ab initio construction of protein tertiary structures using a hierarchical approach. J. Molec. Biol. 300:171-185.

Zhang, C., and S. Kim. 2000. Environment-dependent residue contact energies for proteins. Proc. Natl. Acad. Sci. USA. 97:2550-2555.

Zhang, C., G. Vasmatzis, J. Cornette, and C. DeLisi. 1997. Determination of atomic desolvation energies from the structures of crystallized proteins. J. Mol. Biol. 267:707-726.

Zhou, H., and Y. Zhou. 2002. Distance-scaled, finite ideal-gas reference state improves structure-derived potentials of mean force for structure selection and stability prediction. Protein Sci. 11:2714-2726.

Zhou, H., and Y. Zhou. 2003. Quantifying the effect of burial of amino acid residues on protein stability. Proteins. 54:15-22.

Zhou, H., and Y. Zhou. 2004. Single-body knowledge-based energy score combined with sequence-profile and secondary structure information for fold recognition. Proteins. 55:1005-1013.

[Author Affiliation]

Chi Zhang, Song Liu, Hongyi Zhou, and Yaoqi Zhou

Howard Hughes Medical Institute Center for Single Molecule Biophysics, Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, New York

[Author Affiliation]

Submitted October 14, 2003, and accepted for publication January 20, 2004.

Address reprint requests to Dr. Yaoqi Zhou, Howard Hughes Medical Institute Center for Single Molecule Biophysics and Dept. of Physiology and Biophysics, State University of New York at Buffalo, 124 Sherman Hall, Buffalo, NY 14214. Tel.: 716-829-2985; Fax: 716-829-2344; E-mail: yqzhou@buffalo.edu.

� 2004 by the Biophysical Society

0006-3495/04/06/3349/10 $2.00

Sjostrom and Hanzal lead Coyotes to 4-1 victory over Devils

Fredrik Sjostrom scored twice and Martin Hanzal had a goal and three assists to lead the Phoenix Coyotes over the New Jersey Devils 4-1 in the NHL on Saturday.

Goalie Mikael Tellqvist, a backup since the arrival of Ilya Bryzgalov, made 30 saves in his first start for Phoenix since Nov. 12. He lost the shutout when Zach Parise scored a short-handed goal with six minutes remaining.

Radim Vrbata also scored for the Coyotes, who are 2-1 at the midpoint of a season-high six-game road trip.

The loss ended the Devils' five-game winning streak at home and was only their third loss in the last 13 games.

Stars 4, Sharks 2

At San Jose, California, Mike Ribeiro and Brenden Morrow each had a goal and an assist for Dallas, which has won five straight games in San Jose.

Antti Miettinen scored the go-ahead goal and Steve Ott added an empty-netter for Dallas.

Devin Setoguchi and Patrick Rissmiller had goals for San Jose.

Marty Turco made 16 saves in his 17th win against San Jose in 26 games.

Sabres 3, Blackhawks 1

At Buffalo, New York, Thomas Vanek had a goal and assist, and Ryan Miller made 26 saves to spoil Patrick Kane's homecoming and help lift Buffalo over Chicago.

Drew Stafford and Jason Pominville also scored, and Derek Roy added two assists for Buffalo, which won its third straight.

The game was Kane's first in his hometown. The No. 1 overall pick in this year's draft grew up near the Sabres' downtown arena, and had about 500 family and friends in attendance.

Red Wings 5, Panthers 2

At Detroit, Dan Cleary and Brian Rafalski scored in a 1:04 span early in the third period to break a tie, and Valtteri Filppula converted one of Detroit's two penalty shots in a victory over Florida.

Rafalski added an assist, Pavel Datsyuk also had a goal and an assist, and Johan Franzen had a goal for the NHL-leading Red Wings, 3-for-6 on the power play.

Henrik Zetterberg had two assists, and Chris Osgood made 33 saves.

Olli Jokinen and Radek Dvorak scored for Florida, and Tomas Vokoun stopped 41 shots.

Senators 7, Thrashers 3

At Ottawa, Dany Heatley scored twice, and Antoine Vermette had a goal and two assists in Ottawa's win over Atlanta.

Nick Foligno, Chris Kelly, Joe Corvo and Andrej Meszaros also scored for the Senators, who played their first home game in two weeks. Jason Spezza had two assists.

Ottawa won its fifth straight following a seven-game losing streak. Atlanta has dropped four in a row.

Ilya Kovalchuk scored twice for the Thrashers, and Eric Perrin added Atlanta's other goal. Marian Hossa had two assists in the loss.

Canadiens 4, Maple Leafs 1

At Montreal, Saku Koivu scored twice and Carey Price made 28 saves to lead Montreal over Toronto.

Andrei Kostitsyn and Alex Kovalev also scored for the Canadiens, who had lost six straight at home.

Price, a 20-year-old rookie making his sixth straight start, came within 4:06 of recording his first NHL shutout.

Boyd Devereaux scored for Toronto _ his fifth of the season _ 15:54 into the third period.

Bruins 2, Blue Jackets 0

At Boston, Jeremy Reich scored his first NHL goal and Alex Auld stopped 32 shots for his first shutout with Boston.

Auld, acquired from Phoenix on Dec. 6 after starting goalie Tim Thomas went down with a strained groin, improved to 4-1 with Boston. It was his fourth career shutout and second this season.

The Bruins remained the only team not to lose consecutive regulation games despite getting only 18 shots.

Marco Sturm added an empty-net goal with 11.9 seconds left to ruin Columbus' first visit to Boston since January 2003.

Penguins 3, Islanders 2

At Uniondale, New York, Tyler Kennedy scored the winning goal and added two assists for Pittsburgh, which snapped a two-game losing streak and beat New York.

Sidney Crosby and Ryan Whitney also scored for Pittsburgh, which got 27 saves from Dany Sabourin.

Rick DiPietro stopped 37 shots for the Islanders. Richard Park and Josef Vasicek had goals for New York.

Capitals 3, Lightning 2

At Tampa, Florida, Brian Pothier scored a power-play goal in third period to help Washington beat Tampa Bay.

Thomas Fleischmann and David Steckel added goals, and Brent Johnson made 23 saves.

Paul Ranger and Vincent Lecavalier scored for Tampa Bay, and Johan Holmqvist made 29 saves after being pulled from his previous two starts.

Hurricanes 6, Flyers 5, SO

At Philadelphia, Rod Brind'Amour banked a shootout shot in off the crossbar to lift Carolina.

Brind'Amour's goal came after teammates Matt Cullen and Jeffrey Hamilton traded tallies in the tiebreaker with Philadelphia's Mike Richards and Joffrey Lupul.

Niclas Wallin, who also had an assist, Cullen, Eric Staal, and Trevor Letowski scored in regulation for the Southeast Division leaders, who snapped a three-game losing streak.

Lupul scored three goals _ his second hat trick in three games _ and Scott Hartnell and Danny Briere also scored for the Flyers.

Justice Probes Hiring of Prosecutors

WASHINGTON - The Justice Department is investigating whether its former White House liaison used political affiliations in deciding whom to hire as entry-level prosecutors in some U.S. attorney offices around the country, The Associated Press has learned.

Such consideration would be a violation of federal law.

The inquiry involving Monica Goodling, a conservative Republican who recently quit as counsel and White House liaison for Attorney General Alberto Gonzales, raises new concerns that politics have cast a shadow over the independence of trial prosecutors who enforce U.S. laws.

Justice spokesman Dean Boyd confirmed Wednesday that the department's inspector general and Office of Professional Responsibility have been investigating for several weeks Goodling's role in hiring career attorneys - an unusual responsibility for her to have had.

Investigators are trying to determine whether Goodling "may have taken prohibited considerations into account during such review," Boyd told the AP. "Whether or not the allegation is true is currently the subject of the OIG/OPR investigation."

Three government officials with knowledge of the investigation said Goodling appears to have sought information about party affiliation while vetting applicants for assistant U.S. attorneys' jobs. The officials spoke on condition of anonymity because of the ongoing investigation.

Goodling's attorney, John Dowd, declined to comment.

Separately, senators subpoenaed Gonzales on Wednesday directing him to provide any e-mails related to presidential adviser Karl Rove and the firings of eight federal prosecutors. In Jackson, Miss., Gonzales ended a news conference about the Virginia Tech shootings after he was asked about being subpoenaed.

"I don't want to comment on it without going back and talking to folks within the department," Gonzales said.

Additionally, new documents surfaced Wednesday showing that at least four of the eight targeted U.S. attorneys reported being told to stay quiet about their dismissals by Mike Elston, the top aide to Deputy Attorney General Paul McNulty.

The documents also indicate that one of the fired prosecutors was told by Associate Attorney General William Mercer that the dismissals were to make room for others to gain experience so the Republican Party would have a strong bench of candidates for federal judgeships.

Gonzales - with President Bush's backing - has resisted calls for his resignation in the controversy over the dismissals, which Democrats say appear to have been politically motivated.

Last month, Goodling quit the Justice Department after refusing to testify to Congress about her role in the firings of eight U.S. attorneys. The House Judiciary Committee has voted to give Goodling immunity from prosecution for her testimony - an offer that is being reviewed by the Justice Department to make sure it does not interfere with any criminal investigations.

Chairman John Conyers, D-Mich., said the new investigation "suggests politics infected the most basic operations at the Justice Department."

Goodling and Kyle Sampson, Gonzales' former chief of staff, also had authority to hire or fire about 135 politically appointed Justice Department employees who did not require Senate confirmation.

Asked if he had ever heard of the agency's White House liaison getting involved in hiring of career prosecutors, Dennis Boyd, the executive director of the National Association of Assistant United States Attorneys, said: "No, never." Boyd, who is no relation to the Justice Department spokesman, declined further comment.

The investigation of Goodling appears to focus on her role in reviewing applications for trial prosecutors for offices headed by temporary or acting U.S. attorneys who had not been confirmed by the Senate. That responsibility is usually handled by the Justice Department's executive office of U.S. attorneys.

Goodling had served in the executive U.S. attorney's office until she was transferred to serve as Gonzales' counsel and primary White House contact. The internal Justice investigation concerns Goodling's review of job applicants only after she joined the attorney general's office, the government officials said.

An official using political affiliation in choosing such applicants would clearly violate traditional Justice Department policy and practice, said Joe diGenova, who was the U.S. attorney in the District of Columbia during the Reagan administration.

"There is no justification for it," diGenova said. "Politics should play no role in the decision-making process of career prosecutors. And if it does, that's clearly improper, and clearly a violation of all of the traditional policies in the Justice Department."

Federal law also bars discrimination against employees or job applicants on the basis of political affiliation.

Meanwhile, the House Judiciary panel released new statements from three of the dismissed U.S. attorneys contending they received calls from McNulty chief of staff Elston, admonishing them to keep quiet. A fourth former U.S. attorney, Bud Cummins in Little Rock, Ark., had made a similar accusation in an e-mail released in March.

"I believe that Elston was offering me a quid pro quo agreement: my silence in exchange for the attorney general's," wrote Paul Charlton, the former U.S. attorney in Arizona, according to statements released by the House panel.

John McKay, former top prosecutor in Seattle, said he perceived a "threat" from Elston during his call. And Carol Lam, who was U.S. attorney in San Diego, said that "during one phone call, Michael Elston erroneously accused me of 'leaking' my dismissal to the press, and criticized me for talking to other dismissed U.S. attorneys."

Elston's attorney, Bob Driscoll, said, "There certainly was no intention to threaten anybody."

Daniel Bogden, the former U.S. attorney for Nevada, said he was told he was being dismissed because the Bush administration had a short window to get others into prosecutor jobs to bolster their resumes. President Bush leaves office in January 2009.

Bogden said Mercer told him on Dec. 7, 2006, that the firings were being carried out "so the Republican Party would have more future candidates for the federal bench and future political positions."

Boyd declined to respond.

---

Associated Press writers Laurie Kellman in Washington and Emily Wagster Pettus in Jackson, Miss., contributed to this report.

Mother tells Dr. Phil: Casey Anthony had seizures

ORLANDO, Fla. (AP) — Cindy Anthony said in a television interview that daughter Casey Anthony has a history of seizures, but she is not sure if the condition had anything to do with Caylee Anthony's disappearance in 2008.

The disclosure came during an interview with "Dr. Phil" host Phil McGraw that aired Tuesday.

Cindy and her husband George Anthony spoke with McGraw for a lengthy, taped interview. Another portion of the interview is scheduled to air Wednesday and a part devoted to their daughter's murder trial also will be shown later this month.

Cindy Anthony said that Casey also had a seizure in 2007 and another in 2008 while out on bond following her initial arrest on check fraud charges. She said she is unsure if that condition contributed to her lying to her family and authorities regarding her 2-year-daughter's whereabouts in mid-2008.

"I'm not making justification for (Casey's lies), but there's a cause for that," Cindy Anthony told McGraw. "You just don't have a grand mal seizure."

Casey Anthony's defense attorneys never raised the issue at trial, though late in the case did ask the judge to have doctors examine her to determine if she was mentally fit to stand trial. Three experts ruled her fit and the trial resumed. The reports from their examination were sealed.

Calls by The Associated Press to Anthony's lead attorney, Jose Baez, were not immediately returned.

The toddler was the focus of a wide-ranging search after her disappearance in June 2008. Casey Anthony told police that a fictitious babysitter had kidnapped the child. The 25-year-old maintained the same story to her family until the child's skeletal remains were found in a wooded area in December 2008 not far from the Anthony family home.

Casey Anthony was acquitted of killing Caylee in July, but convicted of four charges of lying to police.

She is currently somewhere in Florida serving a year of probation on a separate check fraud conviction. Authorities are keeping her whereabouts confidential for her safety.

Anthony's acquittal caused a national uproar, with people protesting their displeasure with the verdict both publicly and through social media. It caused so much of a stir that the judge in the case has instituted a cooling-off period before he releases the names of jurors publicly.

The portion of the interview that aired Tuesday centered on what was taking place in the Anthony family before and immediately after they found out from their daughter in July 2008 that Caylee had been missing for a month. McGraw asked them why no red flags were raised in their minds during that time.

"There's hindsight yes, but not in those 31 days," Cindy Anthony said. "... I knew what I know now I would have called the Army, the Navy, anybody."

But McGraw did ask Anthony's parents directly if they thought Casey was responsible for their granddaughter's death. Both said they thought it was strange how calm Casey was when she told them Caylee was missing.

"Well, the last one I saw Caylee with was Casey...In my book, one and one adds up to two," George Anthony said.

He added that as Caylee's mother, his daughter was ultimately responsible for her and that while she was in jail that "I didn't believe 2/3 of what she was telling me. I thought she was keeping her away from Cindy."

The Anthony's were not paid for the interview, but McGraw said that the show is making a donation to a charity begun in Caylee's name to support grandparents' rights and missing and abused children.

понедельник, 12 марта 2012 г.

Orioles rally to beat Royals 4-3 in 10 innings

Nick Markakis singled in the winning run in the 10th inning, giving the Baltimore Orioles a 4-3 comeback win over the Kansas City Royals and split of the two-game series.

Luke Scott hit two solo home runs and Corey Patterson also connected for the Orioles, who snapped a three-game losing streak. Baltimore trailed 3-0 in the fifth inning and 3-2 in the eighth.

On a night when temperatures dipped into the low 50s, the matchup between last-place teams attracted only 9,715 fans, the third-smallest crowd in the 19-year history of Camden Yards. The second-smallest crowd gathered one night earlier.

Julio Lugo got Baltimore started in the 10th with a one-out single off Bryan Bullington (0-1). Patterson walked, and an error by first baseman Billy Butler loaded the bases for Markakis, who hit a liner well over the head of center fielder Mitch Maier.

Alfredo Simon (1-1) pitched 1 2-3 scoreless innings for the Orioles, who denied the Royals their first sweep at Camden Yards since 1998.

Baltimore trailed 3-2 before Patterson hit a solo homer in the eighth off rookie Blake Wood, who had not surrendered a run in his previous four appearances.

Royals starter Zack Greinke allowed two runs and four hits in seven innings. The 2009 AL Cy Young Award winner yielded two homers to Scott but did not allow another runner past second base.

Greinke left with a 3-2 lead, but Wood gave it away.

Orioles starter Kevin Millwood gave up three runs and 10 hits in eight innings. Although the right-hander has gone nine starts without a victory in his first season with the Orioles, he's got a respectable 3.65 ERA and has been victimized by a lack of offensive support.

Millwood retired the first 13 batters before Jose Guillen singled up the middle with one out in the fifth inning. Four of the next five batters hit singles, including RBI hits by Maier, Chris Getz and Scott Podsednik.

Scott homered in the bottom half and again in the seventh. He has nine homers, including six in his last nine games.

NOTES: Orioles RHP Jeremy Guthrie, 3-0 lifetime against Texas, will face the Rangers on the road for the first time since July 2007 in the opener of a two-game series Wednesday night. ... Greinke is 1-4, but has a 2.72 ERA and has left with KC ahead in four of his nine starts.

FDA Approves Amgen's Prolia for Treatment of Postmenopausal Women with Osteoporosis

The US Food and Drug Administration has approved Prolia (denosumab), manufactured by Amgen Inc. (Thousand Oaks, CA), for the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy. Prolia is a 60 mg subcutaneous injection administered by a healthcare professional every six months.

Prolia's approval is based on a pivotal three-year Phase 3 study involving 7,808 postmenopausal women with osteoporosis. Treatment with Prolia resulted in greater bone density, stronger bones, and reduced risk for vertebral, hip, and nonvertebral fractures measured at three years.

Prolia resulted in significant suppression of bone remodeling. The significance of these findings is unknown. The long-term consequences of the degree of suppression of bone remodeling observed with Prolia may contribute to adverse outcomes such as osteonecrosis of the jaw (ONJ), atypical fractures, and delayed fracture healing. ONJ has been reported in patients with Prolia.

Patients should be monitored for these adverse outcomes. The most common adverse reactions (>5% and more common than placebo) were back pain, pain in extremity, musculoskeletal pain, hypercholesterolemia, and cystitis. Pancreatitis also has been reported with Prolia.

Kevin Bowser, Sears Employee

Kevin Bowser, 39, a Sears, Roebuck and Co. junior executive andworld traveler, died Sunday at Michael Reese Hospital..

A South Side resident, he died of natural causes, said hismother, Dorothy Rivers, chief executive officer of the PritzkerGrinker School.

Mr. Bowser had been with the retailer for his entire career. Atthe time of his death, he was an administrative assistant in Sears'employee savings/profit-sharing division. Before that, he served assenior assistant of the organizational behavior section in personneladministration.

A graduate of the Latin School, he developed an interest inforeign relations at a young age. He was selected to participate inan educational program sponsored by the Foreign Study League andattended high school in Britain, France and Germany.

Mr. Bowser then attended Schiller College in Paris. Fluent inFrench and Danish, he spent much of his spare time traveling to suchcountries as Spain, the Netherlands, Italy, Denmark, Belgium,Switzerland and Australia.

The rest of his extra time was devoted to music, particularlythe works of the classical and romantic periods.

He leaves no other immediate family.

Visitation will be from noon to 7 p.m. today at Cage MemorialChapel, 7651 S. Jeffery. Services will follow. Burial will be at9:30 a.m. Friday in Oak Woods Cemetery, 1035 E. 67th.

A.I. Has No Answer for Sixers in Loss

DENVER - Allen Iverson took plenty of shots at his former team, and not all of them during the game. His 30 points weren't enough, however, as Kyle Korver scored 26 points to help the Philadelphia 76ers beat the Denver Nuggets 108-97 Tuesday night in Iverson's first game against his former team.

Iverson was 10-of-24 before getting tossed for his second technical with 1:44 remaining.

Iverson's best shots came before tip-off when he once again ripped the team that traded him to Denver over the holidays, repeating his contention that he should have had more say in the Sixers' style.

The Sixers, who had lost 14 of 16 road games and 19 of their last 23 overall, scored 100 points for the first time in 16 games and improved to 4-4 since the trade that sent Joe Smith and Andre Miller to Philadelphia, along with two first-round draft picks in 2007, for Iverson.

Miller had 17 points and 10 assists against his former team and Smith scored 12 points.

The Nuggets have lost four of six since Iverson's arrival, although he has yet to play with NBA scoring leader Carmelo Anthony and J.R. Smith, the league's top scoring tandem before their suspensions for slugging it out with the New York Knicks last month.

The Sixers, who led by 19 in the second quarter before the Nuggets rallied to tie it at 52 at halftime, led 86-73 after three quarters.

Two free throws, a pull-up 3-pointer and a driving layup by Iverson brought Denver to 86-80 but Steven Hunter's dunk followed by three free throws by Korver - one on an Iverson technical - restored Philadelphia's double-digit lead.

Rookie Yakhouba Diawara scored a season-best 23 points for Denver on the heels of an 0-for-11 shooting performance against Dallas.

After the morning shootaround, Iverson said he felt a player of his stature and tenure should have been listened to when he criticized the Sixers' style of play last month, a condemnation that led to his departure from Philadelphia after 10 tumultuous seasons.

"When you're losing basketball games, 12 of 14, 18 of 20 basketball games, you should listen to somebody because something obviously isn't working," he said.

Iverson said he was still bitter with the way Sixers coach Maurice Cheeks and team owner Billy King handled his complaints that led to his departure from Philadelphia.

Iverson ignored Cheeks on Tuesday night, and he wasn't the only point guard who wasn't exactly eager to see his former coach. Miller walked right past George Karl before the game and didn't even acknowledge him.

"He didn't return calls to me when he played here. Why would he call me now?" said Karl, who counted Miller among his favorite pupils.

Notes:@ There was a moment of silence before tip-off for Darrent Williams, the Broncos' cornerback who was killed Monday. ... Iverson won't get to face the Sixers in Philadelphia this season because the Nuggets made their annual trip there before the trade. ... The Nuggets recalled G Julius Hodge from the Colorado 14ers of the NBA's developmental league. He played in 14 games as a rookie last year before he was wounded in a drive-by shooting and missed the remainder of the season. He entered the game in the final minute for his first action since getting shot last April but didn't record any stats.

Rouble, Patrick (Southern Lakes) Deputy Speaker of the Legislative Assembly

ROUBLE, PATRICK (Southern Lakes) Deputy Speaker of the Legislative Assembly.

B. in Renfrew, Ont. Ed. at St. Lawrence Coll and Royal Roads Univ., Victoria. M. to Sophie Elasoff. Political Career: First elected to the Yukon Leg. g.e. 2002. Private Career: Former Dir: Marsh Lake Advisory Council. Small business owner. Party: Yukon Party. Address: Leg. Office: Yukon Legislative Assembly, Box 2703, Whitehorse, Yukon, Y1A 2C6, (867)667-8641, Fax: (867)393-6252; Email: patrick.rouble@gov.yk.ca.


ROUBLE, PATRICK (Lacs du Sud) Vice-pr�sident de l'Assembl �e legislative. N�� Renfrew, Ont. Fit ses �tudes au Coll�ge St. Lawrence et l'Universit� Royal Roads � Victoria. M. � Sophie Elasoff. Carri�re politique: �lu pour la premi�re fois � la l�gis. du Yukon. �.g. 2002. Carri�re priv�e: Propri�taire-exploitant. Parti pol.: Yukon Party. Adresse: Bureau L�g.: Assembl�e l�gislative du Yukon, CP 2703, Whitehorse, Yukon, Y1A 2C6, (867)667-8641, Fax: (867)393-6252; Courier: patrick.rouble@gov.yk.ca.

Mays, Aaron and `cooperative' biographies

New biographies of Willie Mays and Hank Aaron do nothing to tarnish the reputations of the revered American baseball superstars of an earlier era. The way they were produced, however, illustrates an established niche in U.S. book publishing: cooperative biographies.

Long, and long-awaited, biographies of the two iconic sluggers come out this year, within three months of each other: James S. Hirsch's 600-plus-page "Willie Mays," just released, and Howard Bryant's 600-plus-page book on Aaron, "The Last Hero," scheduled for May.

Mays, who spent much of his career with the New York/San Francisco Giants, and Aaron, a longtime star for the Milwaukee/Atlanta Braves, still are endlessly compared by baseball aficionados, of whom there are many in the United States. Mays normally is celebrated as the more dynamic on-field presence and Aaron as the man who succeeded Babe Ruth as baseball's home run king.

Both books are sympathetic accounts that cover not just Mays and Aaron but the era in which they played, especially how they responded, or did not, to the civil rights movement. Both are black, and their major league careers began within six years of the first black player, Jackie Robinson of the then-Brooklyn Dodgers.

Mays and Aaron, each of whom has published an autobiography, agreed to be interviewed by their respective biographers, although the relationships differed.

Mays was involved from the start and will share in the revenues from the Scribner release, billed as an "authorized" biography. Aaron had not yet agreed to speak to Bryant when the author signed with Pantheon, in 2006. Aaron is not being paid and, Bryant said, did not even see the book before it was finished.

"Luckily, it turned out all right," said Bryant, a senior writer for ESPN.com who has written books on steroids and the Boston Red Sox. "Had he not cooperated, it would have been a very different book."

Biographies of living people generally are either authorized, written with the subject's involvement and to the subject's taste, or "unauthorized," written without the subject's permission and often against the subject's wishes. The most famous unauthorized biographies are Kitty Kelley's best sellers about celebrities including Jackie Kennedy, Frank Sinatra and Nancy Reagan. A Kelley book on Oprah Winfrey is due in April.

In between those stands a category that could be called "cooperative," in which the subject is available but otherwise disengaged. "Cooperative" biographies in recent years have included Gerald Martin's "Gabriel Garcia Marquez: A Life" and Peter Biskind's "Star," about Warren Beatty. The Mays book fits partly, because Hirsch says he was granted full editorial freedom; "The Last Hero" does entirely because Aaron's participation was limited to talking to Bryant.

Bryant said he had been eager for years to write about Aaron, whom he says he first met in 1997 at a tribute for Robinson, the first black major leaguer, who died in 1972. Bryant initially was unable to contact Aaron for the book, learning later that the Hall of Fame member feared the interview would center on Barry Bonds' pursuit of Aaron's career home run title.

Meanwhile, Bryant spoke to friends and acquaintances of Aaron's, including former Presidents Jimmy Carter and Bill Clinton, baseball Hall of Famers Joe Morgan and Reggie Jackson, and former Braves teammates including Joe Torre and Dusty Baker.

"Before I got to Aaron, the best advice I got was from David Halberstam, who wrote a book on Michael Jordan without getting Jordan and a book about Bill Clinton without getting Clinton," Bryant said of the late Pulitzer Prize-winning author and journalist.

"He said to me, `The strategy was very simple _ for every day they didn't talk to me, make three phone calls to other people.' You have to work around obstacles. It was the best piece of advice anyone's given me."

After Bonds overtook Aaron's home run record, in 2007, Aaron opened up to Bryant.

"When Henry and I finally spoke, he was tremendous, he was unbelievably gracious," Bryant said. "He was even somewhat embarrassed someone was taking an interest. He didn't ask for any money. He didn't ask for any review copy of the book. He could have made the one phone call that every author dreads, which is to call all of his people and say, `Hey, this guy is writing a book about me. Don't talk to him.'"

Like Bryant, Gerald Martin began working on his Garcia Marquez book before receiving any assurance that his subject, a Colombian Nobel Literature laureate, would talk to him. When they first discussed the project, Garcia Marquez was reluctant, asking Martin, "Why do you want to write a biography? Biographies mean death."

The author relented eventually and set just one condition: "Don't make me do your work," Martin recalled in the book's foreword. When asked if his book was authorized, Martin likes to respond, "No, it is not an authorized biography. It's a tolerated biography."

As Bryant, Biskind and others have learned, the cooperative book can be the most rewarding and most stressful way of working. It is ideal, because the biographer has freedom and access, and stressful because there is no obligation, contractual or otherwise, to keep the subject from changing his or her mind.

Biskind, known for the Hollywood history "Easy Riders, Raging Bulls," is a contributing editor to Vanity Fair who had interviewed Beatty several times and says he first suggested a biography around 1989-90. Beatty, known for being noncommittal, initially had no answer, then implied he was writing his own book, then called Biskind a couple of years ago and told him to do it. Biskind was pleased, but suspicious.

"He's a movie star and they do what they want. He did this kind of turnaround which I learned later is characteristic of him: He pitched an idea and sort of hooked me, and then he turned around and acted like I had to sell the idea to him," Biskind says. "So we had a series of lunches and phone calls, and I became convinced he would do it."

Deirdre Bair's "Samuel Beckett," awarded in 1981 a National Book Award, is considered a model for the cooperative biography, with the Irish playwright promising that he would "neither help nor hinder," Bair explained recently. In 1971, she had finished a dissertation on Beckett and thought a book would be worth pursuing. She wrote to him in Paris, his longtime residence.

"He replied, `My life is dull and without interest. The professors know more about it than I do. It is best left unchampioned,'" Bair said. "Then he scrawled across the page, `Any biographical information I possess is at your disposal.'"

She remembered her relationship as productive and businesslike, with Bair calling him "Mr. Beckett," and Beckett addressing her as "Miss Bair." A more personal, and difficult bond was formed with a new subject, Simone de Beauvoir, who called her biographer "Deirdre" and had very different ideas about how to "cooperate."

"When we started, she said, "I'll talk. I'll tell you things and then you write them down.' And I sort of put my head in my hands in despair," Bair recalled. "And she said, `What's wrong?' And I said, `That's not how I worked with Beckett.' And she said, `Well, I can't let him get ahead of me. All right, that's how I'll work you, too.'"