Leading scorers in the English Premier League after Saturday's games:
Nicolas Anelka, Chelsea, 13 goals
Robinho, Manchester City, 8
Cristiano Ronaldo, Manchester United, 8
Amr Zaki, Wigan, 8
Robin van Persie, Arsenal, 7
Gabriel Agbonlahor, Aston Villa, 7
…
Rose is a Red,
Cincy fans are blue,
Pete is disabled
And that's new.
Pete Rose will be sidelined on Opening Day as a player for thefirst time in his 23-season career.
The Cincinnati player-manager yesterday went on the 15-daydisabled list to recover from a severe case of the flu.
Rose missed most of the last week of spring training with theflu. He'll be eligible to come off the disabled list April 18.
Rose was placed on the 15-day DL retroactive to Thursday, theday of the first game he missed. The move left the Reds at theagreed 24-man roster limit.
Rose, who turns 45 April 14, had stomach pains for a week …
WEST PALM BEACH, Fla. - A letter from Democratic senators blasting conservative talk show host Rush Limbaugh for using the phrase "phony soldiers" on his program was sold Friday on eBay for a record $2.1 million.
A private foundation made the winning bid, which eBay spokeswoman Catherine England said set a record for the most expensive item sold for charity by the online auctioneer.
Limbaugh's comment during his radio show last month drew broad criticism from Democrats, who said he was smearing soldiers opposed to the Iraq war. Limbaugh and other conservatives responded with outrage of their own, saying Democrats were mischaracterizing comments aimed at one particular …
Herbert G. Klein, Richard Nixon's ex-White House director of communications and a former editor for Copley Newspapers, has died. He was 91.
Klein died Thursday after suffering a cardiac arrest at his home in the San Diego suburb of La Jolla, family members told the Union-Tribune.
Klein became a special correspondent for Copley after serving with the Navy in World War II. He covered Nixon's 1946 congressional campaign for Copley, starting an association that would eventually lead him to the White House.
Klein accompanied Vice President Nixon to Moscow in 1959 for historic meetings with Soviet Premier Nikita …
Narrow loss is harsh but side must improve at the breakdown Matchreport David Anderson email: sport@gazettenews.co.uk OLDCOLFEIANS....... 20 BRENTWOOD ......... 17 (London & South-East Division 1North) A LATE surge from Brentwood wasn't enough to stop theirsecond defeat of the season at Old Colfeians on Saturday.
Director of Rugby Steve Killington was forced to make two changesto last week's winning team. Winger Andy Lloyd replaced Tom Larkinwhile veteran hooker Dave Brook, called up at mid-day, took overfrom Anthony Sherwood. On an extremely hot afternoon Old Colfskicked off into the sun. The first few passages of play belonged toBrentwood's pack as they …
EXCLUSIVE REPORT
IT LEADERS POLLED ABOUT SOFTWARE AS A SERVICE CONFIRM THAT IT DELIVERS ROBUST APPLICATIONS- TYPICALLY AT LOWER COST THAN CONVENTIONAL DEPLOYMENT AND LICENSING MODELS. BUT IMPLEMENTATION IS SLOW IN THE ENTERPRISE CORE, WHERE DATA SECURITY, AVAILABILITY AND EASE OF INTEGRATION REMAIN KEY CONCERNS.
ANDY STEGGLES, CIO OF THE RISK AND INSURANCE Management Society, considers himself a convert to software as a service. It was a very different story 18 months ago, when he was sure SaaS would never work for RIMS' complex systems and the mission-critical data the New York-based professional association had on its 11,000 members around the world.
Steggles …
Detroit 4, Dallas 1
Friday, May 9
Pittsburgh 4, Philadelphia 2
Saturday, May 10
Detroit 2, Dallas 1
Sunday, May 11
Pittsburgh 4, Philadelphia 2
Monday, May 12
Detroit 5, Dallas 2
Tuesday, May 13
Pittsburgh 4, Philadelphia 1
Wednesday, May 14
Dallas 3, Detroit 1
Thursday, May 15
Philadelphia 4, Pittsburgh 2
Saturday, May 17
Dallas 2, Detroit 1
Sunday, May 18
Pittsburgh 6, Philadelphia 0, Pittsburgh wins series …
Peterhead continued their year of rebuilding as Steve Patersontried to mould a team capable of promotion to the First Division.
Inconsistency continued to mar the second part of last season'scampaign, the Balmoor side finishing just two points clear of arelegation play-off spot.
All of this came 12 months after missing out on promotion onpenalties to Partick Thistle.
Paterson, assisted by Neale Cooper, …
Caucus mayor rejects criticism: SKOKIE CAUCUS PARTY; "INCOMPARABLE" SERVICES IN VILLAGE
Skokie Mayor George Van Dusen, running in his first campaign for that office since being appointed to it in 1999, says village residents enjoy "incomparable services", a lower tax levy today than in 1990, and a government which "reaches out to every community" within its boundaries.
In the coming stars he hopes to add to features which make Skokie "a very desirable place to live."
In an interview with the Jewish Star last week, he said that those plans include extending the service of, and improving the facilities at, the Skokie Swift; developing a seniors transit program (similar …
Activists have occupied Turkmenistan's embassy in Paris to demand the release of two journalists held in the Central Asian country.
French Foreign Minister Bernard Kouchner says the activists from media watchdog Reporters Without Borders briefly entered the embassy before leaving peacefully.
The activists were calling attention to the plight of journalists in …
MEXICO CITY -- A tale of nature's revenge, stretching back morethan two centuries and halfway around the world, has come full-circle in a battle of cactus, moth and man.
At stake is the survival of a Mexican national symbol.
The dull-colored cactus moth that reached Mexican territory thissummer threatens to devastate the country's nopals, the prickly pearplant that graces the country's flag and is deeply interwoven in itshistory, culture and diet.
The moth didn't migrate here from its native South America;mankind carried it -- to Australia, South Africa, and finally theCaribbean. That makes it a cautionary tale about the dangers oftransplanting species, …
HOMESTEAD, Fla. - Jimmie Johnson's California cool turned to euphoria when he won the Daytona 500. At Indianapolis, his emotions were overwhelmed again after a win he never expected. Still, Johnson had won races before. A first NASCAR championship? For the driver who had everything but, nothing could have come as a bigger relief.
"It's going to take a little bit of time for this to soak in, just to think what this team has accomplished and the year we've had," Johnson said. "Being a champion, it's the only thing I ever wanted to be."
He finally got his wish Sunday, wrapping up an overdue Nextel Cup title with his ninth-place finish at Homestead-Miami Speedway. It sealed …
PARIS (AP) — France and Britain stepped up calls Monday for other world powers to isolate Libya's Moammar Gadhafi with a no-fly zone, amid diplomatic differences over how much backing to give Libyan rebels.
The accelerated push came as U.S. Secretary of State Hillary Clinton and other top diplomats from the Group of Eight prominent world economies met in Paris for a previously planned foreign ministers meeting.
France, which has angered some allies by offering diplomatic recognition to Libya's opposition, said it is important to act urgently against "barbarity" by Gadhafi's forces.
French President Nicolas Sarkozy and British Prime Minister David Cameron, in an letter to the EU president last week, said they supported "continued planning to be ready for all possible contingencies" in the Libyan situation — "including a no-fly zone or other options against air attacks."
On Monday, Cameron said that time was of essence in responding to the situation in Libya, and NATO was drawing up contingency plans for a no-fly zone.
"Every day Gadhafi is brutalizing his own people. Time is of the essence," Cameron told the parliament in London. "There should be no let up in the pressure we put on this regime."
He added: "No one is talking about invasion or boots on the ground."
Insurgents who control much of eastern Libya have called for a no-fly zone, as forces loyal to Gadhafi strike back with tanks and planes — pressing eastward against the rebels Monday.
British Foreign Secretary William Hague said Libyans will face a "nightmare" if Gadhafi regains control, insisting that the world is "reaching a point of decision" on whether foreign forces will impose a no-fly zone.
Hague also said he "wouldn't exclude" amending a ban on arms exports to Libya so that weapons could be shipped to the rebels — but that talks with allies on that are needed.
The Arab League has backed a no-fly zone, and Hague told BBC Radio Monday that "in cases of great, overwhelming humanitarian need" one could be enforced without a U.N. Security Council resolution.
French Foreign Ministry spokesman Bernard Valero, speaking to The Associated Press, pointed to an "urgency" to act because violence against civilians was increasing in Libya. He said France also was working on a list of sanctions against Gadhafi's regime at the U.N. Security Council.
Other countries, including the United States, have been more cautious.
Germany's foreign minister, Guido Westerwelle, acknowledged that the Arab League supported a U.N.-approved no-fly zone, "but at the same time, it rejected any form of foreign, international intervention."
"These are questions that have to be discussed, these are not clear signals being sent, because a no-fly zone would be a military intervention," he said in Berlin.
Westerwelle said the Arab League would need to "not just support but also participate" in any action beyond targeted sanctions. He also stressed that Germany and other European countries don't want to be drawn into a long-lasting war in North Africa.
Italy, a G-8 member that has close economic ties to Libya, has said it would support a no-fly zone, but is against unilateral actions by its allies. Before flying to Paris, Foreign Minister Franco Frattini said Italy believes the Libyan crisis requires "an immediate cease-fire accompanied by international measures."
He echoed the sense of urgency.
"If these decisions come too late, they nullify the goal of preventing Gadhafi from carrying out a massacre," Frattini said. A no-fly zone could be a deterrent, he said.
Turkish Prime Minister Recep Tayyip Erdogan, however, said that a foreign military intervention would not work.
"We have unfortunately seen from previous examples that external interventions, especially through military means, do not contribute to solutions, on the contrary, they deepen them," Erdogan said. "Therefore, we regard a NATO intervention on Libya or any other country to be extremely useless, and furthermore, we fear that it would yield dangerous results."
___
Geir Moulson in Berlin, Alessandra Rizzo in Rome, Jill Lawless in London and Suzan Fraser in Ankara contributed to this report.
Adams COUNTY
A group of downtown Hanover merchants has begun developing promotions to take advantage of the surge in activity from Main Street events in the community.
Events under the Saturdays on Main Street moniker - which itself began among small-business leaders in the community - started in May with the Chalk It Up Hanover street art festival.
The events have continued to attract people to the downtown as part of a wider, grassroots community development initiative.
Now, some of the attention is shifting to encouraging attendees to spend their money at area shops - some of which have either opened or have moved into the heart of downtown in the past year or so.
The Hanover area's shopping options are not limited to the growing, high-profile cluster of big-box retailers on nearby Eisenhower Drive, said Heather Lunn, co-owner of The Sheppard Mansion and Carriage House Market.
There are more than 30 shops of one form or another in downtown - more than many people might realize - and it is important for them to work together for success, she said.
"It's not just being downtown; it's shopping in (the stores) as well," she said.
The first promotion planned after the merchant group's initial meeting in October was designed to encourage people who come to the borough's holiday parade and related festivities just after Thanksgiving to shop at multiple downtown stores, Lunn said.
Anyone shopping at one business could take his or her receipt to another downtown establishment and receive a discount or other giveaway, she said. The Carriage House offered a 20 percent discount on items in the market, for example, Lunn said.
The promotion ran the Friday and Saturday after Thanksgiving in tandem with the borough's holiday happenings, Lunn said. It also is planned for today and Saturday.
About 90 percent of the merchants contacted about the promotion agreed to participate after Thanksgiving, and most of the rest usually aren't open for Black Friday in the first place, she said.
The promotion and shopping activity went well, though some people hit the big-box retailers early and were shopped out by the time they got to the downtown stores, Lunn said.
Helping to encourage people to spend money locally is an outgrowth of the philosophy of the Carriage House Market, which began in 2010 as an outlet for locally grown food and Pennsylvanian- crafted gifts, Lunn said.
The Sheppard Mansion began first as the answer to what the family could make out of the family home of Lunn's great grandparents instead of selling it more than 10 years ago.
It started as a bed-and-breakfast, and in 2005 the owners added a restaurant that is focused to the "point of obsession" on serving local fare, he said.
It especially is important in a poor economy for people to spend their money locally and help their neighbors, Lunn said.
Downtown foot traffic is part of what Taryn Gerrick said encouraged her to move the pet store she owns with her fianc� into downtown about four months ago.
Jocelyn's Puppies & Pet Supplies, which was named for her fianc�'s daughter, opened on York Street more than two years ago out of a love they have for pets, Gerrick said.
The new site on Carlisle Street offers a bigger store in what she called a well-known area of Hanover, and the business is doing well since the move, she said.
Helping more people become aware of all of the downtown business offerings underpinned the formation of the Saturdays on Main Street committee from a previous business group that formed about a year ago.
Efforts continue with Black Friday-related events that included a scramble in which participants received a list of clues for things they had to find downtown, said Pam Brown, chairwoman of the Saturdays on Main Street committee.
Brown, who also owns the borough's On The Go Caf� & Catering Co., said the community is usually packed with people for holiday festivities each year, but they leave too quickly.
Merchants joke that they should put up barricades to help keep them in town, so the cross-promotion with area businesses is a great addition to the downtown promotional efforts, she said.
"We all have customer base, but they tend not to go to the next store," Brown said.
[Sidebar]
"We all have customer base, but they tend not to go to the next store."
Pam Brown, On The Go Caf� & Catering Co.
[Author Affiliation]
By Brent Burkey
brentb@journalpub.com
DAMASCUS Fundamentalist Muslim kidnappers freed American JosephCicippio today, and the long agony of Western hostages seemed closeto an end.
Two Americans, journalist Terry Anderson and academic AlannSteen, are expected to be released within a week.
Iran, which has ties with the kidnappers, said a UN-mediated "noreprisals" deal had been reached and Germans Heinrich Struebig andThomas Kemptner will be freed soon, too.
Cicippio, 61, emerged from more than five years in captivitylooking thin and weary. He told reporters his kidnappers had rushedhim to a hospital two months ago for stomach surgery.
Cicippio, deputy comptroller of the American University inBeirut, was threatened three times with execution by his captors.
"I am happy it's all over and I would like to put it all behindme," he said. "I would like to get on to the first day of my newlife."
He was reunited with his wife, Elham, and her mother at the homeof the U.S. ambassador to Syria, Christopher Ross.
A U.S. military plane later took off with Cicippio and his wife,bound for the U.S. military hospital in Wiesbaden, Germany, that hasbeen a routine stopping point for newly released American hostages.
Cicippio's sons, David and Eric; his brother, Thomas, andThomas' wife, Frances, were scheduled to leave Philadelphia forGermany later today.
UN hostage mediator Giandomenico Picco made a rare publicappearance when Cicippio was handed over at the Syrian ForeignMinistry.
Picco has been slipping in and out of Middle East capitals forfour months to arrange a swap of Western hostages and other captives.
His mission may be nearly finished, according to statements fromthe kidnappers and governments ranging from Iran to Israel.
The United Nations itself is more cautious. A statement Sundaynight spoke of "important progress" and of a pledge made to Picco.
Iran, where an Islamic revolution fostered the anti-Westernpassions behind the Lebanese kidnappings, says a comprehensiveagreement, including promises that hostages' nations would notretaliate against the kidnappers, was reached in Damascus Saturdaynight.
Picco's mission began in August when freed Briton John McCarthyand American Edward Tracy asked UN Secretary-General Javier Perez deCuellar to mediate a general exchange.
Since then, Americans Jesse Turner and Thomas Sutherland andBritons Jack Mann and Terry Waite have been released, and Israel hasfreed 91 Arab prisoners.
There are two bills in Congress now that could potentially put considerable new resources into communities with high unemployment around the country to create jobs. The first is the $118 billion' bill, H. R. 4231, that is essentially designed to extend unemployment insurance and provide tax incentives to companies to create jobs. That is being put on the fast track to pass before politicians leave for the recess in June to campaign for re-election.
The second bill on the horizon however, is H. R. 4812 the Local Job Creation Act, a more far reaching bill that is the subject of a major effort by the Congressional Black Caucus to get groups mobilized to support it It is an important piece of legislation because it sends funds to localities targeted to places with high levels of unemployment and poverty.
A major recipient of such funding will be !ocal government, not state governments, and a unique recipient will be non-profit community organizations that engage in local job creation. The Leadership Conference on Civil Rights recently sponsored a forum on Capitol HUl in collaboration with the CBC that featured mayors and economists, but also representatives of ihe unemployed, poor and homeless who told their stories. It built a strong foundation for the support of H.R.4S12.
The importance of this legislative proposal is that it breaks with 30 years of ineffective urban policy. When Ronald Reagan came into office, cities were put on the backbumer of public policy because they were associated with Blacks who were becoming majorities and producing local officials.
So. the conservatives did not want to recreate President Lyndon Johnson's Great Society approach of funding Model Cities or a War on Poverty. Most of the money went to corporations large and small, to train inner city residents and employ them. in return, they became exempt from billions of dollars of taxes for creating jobs in what became known as Empowerment or Enterprise Zones. While Bill Clinton sent 1JiIOO million to six big ciiies (Chicago. New York. Detroit, Los Angeles, and Atlanta), businesses received $17 billion 2002-2009).
However, in 2005 a critical study by Harvard University for the U. S. Department of Commerce surveyed these programs and found that they produced very little economic development in cities that benefited disadvantaged populations. There has been substantial agreement with its findings by researchers at the Brookings Institution, the Urban Institute and other authoritative organizations since 2005.
It is time for the White House Office on Urban Affairs to go back to what worked. Lyndon Johnson's approach of direct funding for job creation helped to create a new Black middle class which CUE the poverty rate from 50 percent in 1 9CiO to 30 percent by the end of that decade. But like any bill that has the hint of spending money on people who need it most, the Blue Dog Conservative Democrats are opposing it unless it is paid for, that it means it must abide by the "pay-go" rule. However, Rep. Barbara Lee, is leading the CBC in trying to have this effort declared an "emergency" so that it does not have to conform to the Pay-go rules.
Blacks and others who live in the Congressional Districts of conservative Democrats must finally challenge them. For example, I previously have mentioned John Barrow, a leader of the Blue Dog coalition in the House, whose district (Georgia 12} has a 45 percent Black population. But there are other Blue Dog districts with over 30 percent Black population, such as: Jim Marshall Georgia 13, John Spratt S Carolina 5, and Bob Etneridge N Carolina 2. With these healthy Black populations, how is it that they are unable to put pressure on these representatives to support H. R. 4812?
This legislation represents a prime large! for all of those organizations, the churches, Greek letter, civic and others who would become active in helping the Black community to pull out of this crisis, not only in the short term, but potentially in the long run.
The force of this struggle must be large enough to break through the conservative strangle hold on human needs public policy to show that there is a much larger constituency for the pain being felt by most Americans right now and that they do not privilege the size of the deficit over that pain. They never have.
[Author Affiliation]
Dr. Ron Walters is an author, political analyst and Professor Emeritus at the University of Maryland College Park.
IN a county where unemployment is just under 8 percent, it isdifficult to comprehend why excellent blue-collar jobs go unfilled -but some of them do.
That's because manufacturers in the area face a shortage ofskilled workers, Karen Price, president of the West VirginiaManufacturers Association, told students at the University ofCharleston Graduate School of Business.
"We have an aging population," Price said. "In the KanawhaValley, the entire work force for manufacturing is going to retire.Eighty to 100 jobs a year will need to be replaced in the chemicalindustry."
Manufacturers can find people with advanced degrees.
"Where we're having trouble is getting the skilled trades," shesaid. "We have kids coming out of high school who can't do simpleninth-grade math - kids who can't add two fractions with the samedenominator."
But it is not just general education students who struggle. About60 percent of college students must take remedial classes in theirfreshman year.
"This is not just in West Virginia," she said. "It's across thecountry. We think we need to start working with the school systems.We've never done that before. We've spoken to school counselors."
Not everyone should go to college. Many people make good money ascarpenters, plumbers, mechanics or chemical industry workers.
These skills are needed, and other states are taking steps tofill the need for them.
"We can't wait five years," she said. "Virginia and NorthCarolina are ahead of us. We've got to have the skills here.
"One of my members said: 'Don't worry about tax policy. If wedon't have skilled people here, they'll pull the production lineout.' "
This is a very real problem that the Legislature, schoolofficials and employers must address.
St. Benedict presented sixth year coach Joe Cullotta with his100th career victory (100-41) as the Rebels (7-5, 4-0) beat Ridgewood61-43 Wednesday in the Chicagoland Prep conference.
Sophomore Carolina Reyes (18 points, 12 rebounds, four steals)led the Rebels. Kim Burke added 15, Denise Hamilton 10. Ridgewood (3-6, 2-1) was led by freshmanPatti McGough's 13 points.
Robeson 48, Phillips 36: Point guard Michelle Brownlee had 22points, four assists and four steals for Robeson (8-1, 4-0), whichwon the battle for first place in the Red Central.
Crane 57, Wells 43: Crane (6-5, 4-0) overcame a 27-17 halftimedeficit in the Blue West behind Carla West (17 points).
Young 95, Westinghouse 31: E.C. Hill had a triple-double (30points, 15 assists, 11 steals) for No. 1 Whitney Young (7-1, 1-0) intheir Red West opener.
Marshall 118, Collins 11: Kenya Pittman scored 24 as defendingClass AA champion Marshall (6-0, 1-0) romped.
Lane Tech 63, Von Steuben 31: Lane (5-2, 4-0) kept its share ofthe lead in the Red North behind Nilda Molina (16 points).
Lincoln Pk. 66, Mather 49: Lincoln Park (6-0, 4-0) won in theRed North behind Audrey Frankin (24 points).
R-B 50, Trinity 34: Leslie Smith scored 17 and Monica Senese 16to lead Riverside-Brookfield (2-9).
Clemente 41, Juarez 37: Trailing 25-13 at the half, Clemente(1-2) rallied behind Shantay Kelly's 29 points. Juarez' Mary JaneCazares scored 25.
Dunbar 62, Du Sable 52: Celestine Jones scored 30 and had sixrebounds for Dunbar (5-4, 3-1) in the Red Central. Freshman TenaeLee had 19 for Du Sable.
Calling cancer a "disease of mass destruction," the Rev. Jesse L. Jackson Sr., Cook County Board President John H. Stroger Jr. and others have joined forces in declaring war against cancer in the Black community.
Jackson urged parents to meet him 9 a.m. Saturday at the Dr. King Workshop, 930 E. 50th St., where they'll be able to get free cancer, diabetes and prostate tests. For the past three weeks including over the weekend, Jackson has worked hard at fashioning partnerships between the Rainbow PUSH Coalition, Stroger, and the American Cancer Society in sharing the responsibility of letting Blacks know about cancer and how it disproportionately affects this population.
During a press conference held at Dr. King's Workshop, 930 E. 50th St., over the weekend, Jackson, who was joined by a number of health officials including Stroger, Diana Hackbarth, R.N., Ph.D., for the campaign for a Healthy Smoke-free Chicago who chairs the Illinois Coalition Against Tobacco, Dr. Clement Rose, vice president of the American Cancer Society Illinois Division, Joel Africk, CEO, American Lung Association of Metropolitan Chicago, announced they're marching in the Loop near City Hall urging aldermen to pass the clean indoor air bill.
"Second-hand smoke takes a terrible toll on our community...," said Hackbarth. "Second-hand smoke is the third leading cause of preventable death in America today, and kills more than 200,000 Illinoisans every year."
"We are aware that second-hand smoke contains more than 4,000 chemicals and 63 carcinogens," she said saying this smoke causes numerous illnesses.
Cancer, Jackson said, disproportionately affects African Americans. He said "changing lifestyles can change life options" and urged Blacks to change their diets.
"A belly full of grease and some pills" is a recipe for death," he warned.
"This year, 133,000 African Americans will pay a doctor to say "you have cancer." That's not necessarily a death sentence.
"If the detection is early enough, then life options are greater. Early detection is a factor," he said. Jackson said 63,000 Blacks will die of cancer this year which is more than the 55,000 soldiers who died in the Vietnam War.
"In Illinois, 5,000 will die from cancer, but, the good news is that these numbers can be dramatically reduced," he said urging early detection. That's why he offered the public free cancer screenings over the weekend including mammograms, prostate tests, and diabetes.
Jackson, who last Friday held a press conference at the John H. Stroger Jr. Hospital, 1901 W. Harrison, and again Saturday at Dr. King's Workshop, 930 E. 50th St., said: "We're going church-by-church... to political leaders and disc jockeys to get the message out.
"We know that diet... obesity is a factor, and smoking is a huge factor." He urged the aldermen and Daley to "take the bold move that NY took and eliminate smoking in our environment... and public places...."
Jackson has also teamed up with the American Cancer Society of Illinois having declared war on cancer during the National Minority Cancer Awareness Week.
Jackson joined Dr. Clement Rose, vice president of the American Cancer Society Illinois Division, Steve Derks, CEO and other officials during yet another press conference held at the Bank One Plaza, Midday Club 56th Floor, 21 S. Clark St.
Also, Jackson said all youth wanting to attend college and have every thing except money, should meet him at 9 a.m. Saturday at the PUSH headquarters.
"We're building a PUSH for Excellence Scholarship Bank," said Jackson. "We want to sign them up Saturday morning to try to connect them up with scholarship."
In creating the alliance to reduce Black cancer deaths, Jackson said they're trying to eliminate the "unjust cancer burden shouldered by racial minorities, the poor and undeserved communities in Illinois."
According to the American Cancer Society (ACS), Blacks have the highest death rate from cancer than any other racial or ethnic group in the nation.
Just in Illinois, officials said Black male mortality rates from cancer are 50 percent higher than those of their white peers and mortality rates from cancer for African American women are 30 percent higher than those of white women.
Data from the ACS show that in 1999, 6,793 Blacks were diagnosed with cancer in Illinois and 3,664 died of the disease which is almost ten lives lost to cancer each day.
Officials said for a five-year period from 1995 to 1999, 13,759 Black women were diagnosed with cancer in Cook County. The number of Black men diagnosed with cancer during the same period was 14,902.
The partnership will be announced today during the reception which kicks off the national Minority Cancer Awareness Week.
Both groups as well as Stroger are uniting to reduce Black cancer deaths by promoting early detection screenings, prevention education, physical fitness, and nutrition programs aimed at meeting the needs of the Black population.
Jackson said common cancers affecting Blacks for males include prostate (39.0 percent), lung (15.5 percent), colon (9.4 percent), females: breast (31.3 percent), and lung (13.1 percent), colon (13.0 percent).
Jackson, who was on WVON's Cliff Kelley Show, said this initiative will build on his "1,000 Churches" model that focuses on economic literacy.
He said 88 churches are currently enrolled and that the ministers will be teaching their flock about the importance of cancer awareness including education, early detection and prevention.
"Despite significant progress in the prevention, detection and treatment of cancer, today's health advances have not benefited all Americans equally, especially African Americans," said Rose.
Reportedly, the higher death rates among Blacks are blamed, in part, on the lateness of the disease being diagnosed and after it has metastasized to distant sites which leaves fewer options for long-term survival, Rose said.
ABSTRACT We present density-functional molecular dynamics simulations of FeP(Im)(AB) heme models (AB = CO, O2, Im = imidazole) as a way of sketching the dynamic motion of the axial ligands at room temperature. The FeP(Im)(CO) model is characterized by an essentially upright FeCO unit, undergoing small deviations with respect to its linear equilibrium structure (bending and tilting up to 10 deg and 7 deg, often occur). The motion of the carbon monoxide ligand is found to be quite complex and fast, its projection on the porphyrin plane sampling all the porphyrin quadrants in a short time (~0.5 ps). Simultaneously, the imidazole ligand rotates slowly around the Fe-N^sub E^. bond. In contrast to carbon monoxide, the oxygen ligand in FeP(Im)(O2) prefers a conformation where the projection of the O-O axis on the porphyrin plane bisects one of the porphyrin quadrants. A transition to other quadrants takes place through an O-O/Fe-N^sub P^ overlapping conformation, within 4-6 ps. Further details of these mechanisms and their implications are discussed.
INTRODUCTION
The reaction of carbon monoxide and 02 with the heme iron of myoglobin (Mb) and hemoglobin (Hb) has long been a topic of discussion and debate (Springer et al., 1994; Olson and Phillips, 1996; Sage and Champion, 1996; Ormos et al., 1998). Of special interest are the properties of the Fe-CO and Fe-O2 units, due to their possible relation with the protein function mechanisms. In this respect, the structure and vibrational properties of the Fe-CO and Fe-O2 moieties have often been used as a sensitive probe for heme-ligand binding and for electrostatic interactions in the distal pocket (Hirota et al., 1996; Unno et al., 1998). The structure of the Fe-CO unit, in particular, was thought from an early stage to be relevant for carbon monoxide binding control (Stryer, 1995), although the quite large distortions reported in x-ray studies (Cheng and Schoenborn. 1991; Yang and Phillips, 1996) have been challenged (see, for instance, Ray et al., 1994; Slebodnick and Ibers, 1997). Spectroscopic studies (Lim et al., 1995; Sage and Jee, 1997) give a much smaller distortion (~7 deg deviation from linearity) and theoretical calculations have demonstrated that the energetic cost for such a small deformation is marginal (Vangberg et al., 1997; Rovira et al., 1997; Spiro and Kozlowski, 1998; Havlin et al., 1998). In addition, experiments on isolated heme models have been undertaken with success (Collman, 1997, and references therein). However, little is known on dynamic aspects like the distribution of the carbon monoxide orientation at room temperature, which could help in the modeling of the experimental data.
The Fe-O bond exhibits a bent end-on geometry both in MbO^sub 2^ and HbO^sub 2^ (Shaanan, 1982), as it is also found in isolated hernes (Jameson et al., 1978). Neutron and x-ray diffraction measurements have found that the 02 is hydrogen-bonded with the N^sub epsilon^-H of His-64 in both MbO^sub 2^ and alpha-Hb (Phillips and Schoenborn, 1981; Shaanan 1983). However, there is no evidence of a hydrogen bond in Beta-HbO^sub 2^, where free rotation of the ligand around its equilibrium position is expected (Shaanan, 1993). Recent electron paramagnetic resonance measurements in cobalt-substituted Hb (in both alpha and Beta subunits) have found evidence of O2 rotation (Bowen et al., 1997). Evidence of O2 rotation is also provided by investigations of synthetic models. In particular, the fourfold disorder found in the crystal structure of picket-fence oxygen systems (Jameson et al., 1978, Collman, 1997) has been interpreted as a dynamic 02 Motion by both M6ssbauer and nuclear magnetic resonance experiments (Spartalian et al., 1975; Mispelter et al., 1983; Oldfield et al., 1991).
The thermal motion of imidazole axial ligands has also been investigated by electron paramagnetic and nuclear magnetic resonance spectra in proteins and synthetic models in homogeneous solution (Nakamura et al., 1996; Momot and Walker, 1997). In the heme proteins, the imidazole is constrained by covalent bonding to the protein backbone. However, in synthetic heme models, it appears to rotate freely and adopt a variety of orientations.
To understand the relation of these motions to the properties of the protein, it is necessary to transcend a purely static point of view and fully examine the influence of thermal fluctuations. This is the objective of the present study, in which first-principles molecular dynamics (MD) will be used to extract information on Fe-CO, Fe-O^sub 2^ and Fe-imidazole motion in FeP(Im)(O^sub 2^) and FeP(Im)(CO) models at room temperature. This study is part of our investigation into ligand binding properties of heme models (Rovira et al., 1997; Rovira and Parrinello 1999). To the best of our knowledge, it is the first study in which the heme-ligand dynamics is examined from first principles.
THE COMPUTATIONAL METHOD
A detailed description of the Car-Parrinello method can be found in several publications (Car and Parrinello, 1995-, Galli and Parrinello, 1991). The calculations were performed with periodic boundary conditions, using an orthorhombic supercell of dimensions a = b = 15 Angstrom, c = 12 Angstrom [FeP(lm)(CO)J and a = b = 15 Angstrom, c = 10 Angstrom (FeP(Im)(O^sub 2^)]- We used the generalized gradient-corrected approximation of spin-dependent density functional theory, following the prescription of Becke (1986) and Perdew (1986). The electronic wave functions were expanded in plane waves up to a kinetic energy cutoff of 70 Ry. Martins-Troullier norm-conserving pseudopotentials were used (Troullier and Martins, 1991), supplemented with nonlinear core corrections for the iron atom (Louie et al., 1982). This is the same setup as we used for the study of structural and equilibrium properties of related heme models (Rovira et al., 1997; Rovira and Parrinello, 1999). The deuterium mass for the hydrogen atoms was used in the dynamic simulations, which allows the use of a longer time step (0.121 fs). The fictitious mass of the Car-Parrinello Lagrangian was set to 700 au. The four meso hydrogens of the porphyrin were kept fixed, because almost all experimental heme models contain bulky substituents in this position. The initial configurations were taken as an overlapping O-O/Fe-N^sub P^ conformation in the case of the O2 complex and the minimum energy structure in the case of the carbon monoxide complex. The systems were allowed to evolve during 2 ps to achieve vibrational equilibration and to lose information of the initial configuration. Further methodological details can be found in Rovira et al. (1997).
RESULTS AND DISCUSSION
Static properties
Detailed information on the structure and electronic properties of FeP(Im)(XY) complexes (XY = CO, O^sub 2^) can be found in our previous work (Rovira et al., 1997; Rovira and Parrinello, 1999) and in several other theoretical studies of heme models (for instance, Dedieu et al. 1983; Jewsbury et al., 1994; Nagatsuji et al., 1996; Vangberg et al., 1997; Havlin et al., 1998; Maseras, 1998; Spiro and Kozlowski, 1998; Sigfridson and Ryde, 1999). Here, we just briefly recall the main stereochemical properties of these complexes. Both systems have a quite similar structure, except for the Fe-XY unit. As depicted in Scheme 1, carbon monoxide binds linearly to the iron, whereas O^sub 2^ prefers a bent end-on type of bond (<Fe-O-O = 121), with the O-O projection on the porphyrin plane bisecting one of the porphyrin quadrants (Rovira et al., 1997). The energetic cost for just a small distortion of the Fe-CO bond is very small: a 7 deg deviation of the Fe-CO angle involves less than one kcal/mol; however larger deviations (>= 15 deg) are prohibitive (Vangberg et al., 1997). Small changes in the Fe-O-O angle can also be made at a small energetic cost, although the change to an upright Fe-O-O is costly in terms of energy (15 kcal/mol) and involves a change of spin state (from singlet to triplet) (Rovira and Parrinello, 1999).
Additional calculations were performed to explore in more detail the shape of the potential energy surface of the FeP(Im)AB systems (AB = CO, O^sub 2^) with respect to the axial ligand position. The structure of the FeP is kept fixed in a planar configuration. The orientation of the axial ligands with respect to the porphyrin was kept fixed at the orientations of interest (see Fig. 1), while the remaining degrees of freedom were optimized. The imidazole ligand was oriented either along the bisector of the NP-Fe-N^sub p^ angle (Fig. 1 a) or overlapping a Fe-N^sub p^ bond (Fig. 1 b). Concerning the diatomic ligands, only the orientational configuration corresponding to the potential energy surface minimum was considered for carbon monoxide (Scheme 1). In the case Of O^sub 2^, which at equilibrium is bent (Scheme 1), the orientational configurations of Fig. 1 were calculated.
From these calculations, we can infer that, for both carbon monoxide and O^sub 2^, the energy is insensitive to the imidazole orientation. In the case Of O^sub 2^, there is an energy barrier of 1.3 kcal/mol (independent of the imidazole rotation) when the O2 is oriented along a Fe-N^sub p^ bond (Fig. 1, a1, b1, b2). Additional calculations relaxing all degrees of freedom gave a value of 1.2 kcal/mol for this barrier, which indicates that also porphyrin distortions will not affect the torsional motion of the ligand. This splits the system into four essentially equivalent porphyrin quadrants.
Given the small energy barrier for O2 rotation around Fe-O, and considering that the torsional mode associated with this motion should have a very low frequency, jumping of the O^sub 2^ from one porphyrin quadrant to another at room temperature is expected to occur in a timescale of a few picoseconds. We should finally point out that the above results do not change significantly regardless of whether the system is in an open-shell or closed-shell electronic state (O-O = 1.29 Angstrom, <Fe-O-O = 122 deg, Fe-O = 1.74 Angstrom at the minimum structure). Thus, for computational reasons, we decided to perform the simulations on the closed-shell surface of this system. It is also worth noting that the above structure/energy relations and the main equilibrium properties of both carbon monoxide and O^sub 2^ models are quite similar to those found for picket-fence systems (Rovira and Parrinello, 1999). Thus, we expect that the conclusions drawn here can also be applied quantitatively to cases that are as yet unmanageable with first-principles MD.
Heme-CO dynamics
An MD simulation of FeP(Im)(CO) (Fig. 2) was performed for a total period of 18 ps, with an average temperature of 300 K. The Fe-N^sub epsilon^ was constrained to its equilibrium value (2.08 Angstrom) during an initial time interval of 2 ps after equilibration of the system.
The most salient features that can be observed from the ligand dynamics is the fast complex motion of the carbon monoxide and the much slower motion of the imidazole. As a way to display the motion of the carbon monoxide ligand, we monitored the projection of the carbon and oxygen atoms on the average plane defined by the four porphyrin nitrogens (hereafter referred to as the N^sub p^ plane). Figure 3 shows the trajectory of both carbon and oxygen projections on this plane. The iron atom is located at the center of each plot, with the x and y axes aligned with the Fe-N^sub p^ bonds (see Fig. 2). As shown in Fig. 3 A, the trajectory of the carbon atom appears to be rather complex and it is concentrated around the iron atom. The trajectory of the oxygen atom (Fig. 3 B) has similar features but is more spread (~0.4 Angstrom from the center). Nevertheless, it should be noted that, with respect to the size of the porphyrin (Fe-N^sub p^ = 2.02 Angstrom), the whole spread of values shown in Fig. 3 B corresponds to just a very small area over the iron atom. Further analysis of the time evolution of the carbon monoxide orientation (data not shown here) reveals that the projection of the C-O axis on the porphyrin plane visits all the porphyrin quadrants in a very short time (~0.5 ps). Therefore, the global picture that can be inferred from our simulation is that of an essentially upright Fe-CO unit, with the carbon monoxide ligand undergoing a fast complex motion within a very small region around its equilibrium position.
Deviations of the Fe-CO unit from its linear equilibrium structure are commonly described in terms of the Fe-C-0 tilt (delta^sub c^) and bend (Theta^sub o^,) angles (Collman, 1997; Schlichting et al., 1994; Yang and Phillips, 1996), depicted in Fig. 2, which have been traditionally related to the protein discrimination for carbon monoxide. The frequency distribution of the delta^sub c^ and theta^sub o^, angles obtained from our dynamics is shown in Fig. 4 A. Small fluctuations of these angles during the MD simulation are quite frequent: delta^sub c^ <= 5 deg, theta^sub o^ <= 8 deg, but larger deformations are unlikely to occur. This is consistent with the results of static calculations (Vangberg et al., 1997; Rovira et al., 1997; Havlin et al., 1998), which have predicted that small delta^sub c^ - theta^sub o^ variations raise the energy of the system by less than 1.5 kcal/mol, approximately the thermal energy available to the Fe-CO moiety.
However, we should point out that, given the complex motion of the ligand described above (Fig. 3), the instantaneous carbon monoxide position cannot be easily defined only in terms of the 5c and 0,, angles. To further illustrate this point, we characterized the trajectory of the carbon monoxide using the 8, and 8. angles defined in Fig. 2. Note that the case 80 > bc corresponds to an in-phase combination of the two angles (i.e., outward bending of the carbon monoxide). As shown in Fig. 4 B, these conformations are the most frequently observed. However, those characterized with an inward bending (50 < 5,) also contribute significantly to the carbon monoxide motion. Therefore, care should be taken when labeling the structure of the Fe-CO unit with the conventional in-phase combination of 8, and 00 angles. The problem should be best regarded as that of a highly dynamic Fe-CO moiety, sampling many different conformations with different probability in a short time.
Concerning the movement of the imidazole, it is dominated by the rotation around the Fe-NE bond and is much slower: while Im rotates 1800 from its initial position (which takes place in one ps) the carbon monoxide samples all porphyrin quadrants. No correlation was observed between the motion of the two axial ligands, as to be expected from the static calculations reported in the previous section. Both clockwise and counterclockwise types of rotation are found, with frequent changes from one to the other mode of rotation and without a clear preference for either an overlapping or bisecting conformation with respect to the Fe-NP bonds (Fig. 1, a and b, respectively). Simultaneously, the porphyrin ring undergoes large amplitude out-of-plane displacements (up to 0.9-A displacements of the pyrrolic carbon atoms are observed). Many peculiar modes of vibration are excited, like a boat distortion and ruffling of the porphyrin ring.
Heme-02 dynamics
An MD simulation for the oxygen analogue, FeP(Im)(02), was performed for a total time of 15.5 ps. As for the carbon monoxide complex, our main interest was to characterize the dynamic motion of the 02 and imidazole axial ligands. To define the orientation of the 02 with respect to the porphyrin plane, we have used one NP-Fe-01-02 torsional angle (phi) and the projection of the O^sub 2^ center of mass on the average porphyrin plane.
The evolution of the phi angle during the MD simulation is presented in Fig. 5. During the first period of the simulation, the 0-0 axis projection on the porphyrin plane lies on the first porphyrin quadrant (1) but undergoes large oscillations between the Fe-N, and Fe-N^sub 2^ bonds. After 2.2 ps, the 02 jumps over the Fe-N^sub 2^ bond toward the second quadrant. Apparently, the energy accumulated in the Fe-O^sub 2^ rotational mode is high enough for the ligand to skip the second and third quadrants and end up in the fourth quadrant (I --> IV, counterclockwise). Two more transitions take place at 8 ps (TV - III) and 13.5 ps (111 ---> IV). All transitions take place via rotation of 02 around the Fe-O axis and involve a conformation with a more open Fe-0-0 angle (124 deg) and the Fe-O bond slightly tilted (3-5 deg ) with respect to the z axis. The Fe-02 tilt (delta) and Fe-0-0 angle (theta) show oscillations similar to the ones found for carbon monoxide (delta <= 10 and 0 = 117-130, as shown in Fig. 6). It is at one of these oscillation maxima that the transition takes place. Therefore, our results provide evidence for the Fe-02 dynamic motion proposed to explain the fourfold disorder found in the crystal structure of picket-fence oxygen systems (Jameson et al., 1978, Collman, 1997). They also confirm the fact that the O-O/Fe-N overlapping configuration is the transition state for the dynamic motion of 02 between the porphyrin quadrants (Spartalian et al., 1975; Mispelter et al., 1983; Oldfield et al., 1991).
Concerning the motion of both axial ligands, we do not observe any correlation between the movement of the 02 and the conformation of the imidazole (for instance, complete fixing of the Im position for 0.5 ps during the second picosecond of the simulation did not change the evolution of the 02 motion), as it was found in the case of the carbon monoxide analogue. The conformation of Im at each jump (i.e., when the 0-0 axis overlaps one Fe-N^subp^ bond) is very similar to al, b2, al, and al for the first four jumps, respectively (Fig. 1). The last transition (111 ---> IV) is characterized by an almost eclipsing conformation of the imidazole similar to b L
It is important to note that the limited time sampled in the simulation precludes a rigorous statistical analysis of the rotational motion of O^sub 2^ about the Fe-O bond and the one of Im with respect to Fe-N.. However, it is expected that, for longer times, the axial ligands would sample all porphyrin quadrants with equal probability. Thus, as a way to enhance our signal, we averaged our data over the porphyrin symmetry operations. Figure 7 A shows the probability distribution corresponding to the 02 center-of-mass projection on the porphyrin plane. For the sake of comparison, the same type of distribution for the carbon monoxide ligand is shown (Fig. 7 B). In the case of carbon monoxide, the distribution is characterized by having a probability maximum for a small region around the iron. In contrast, the distribution for the 02 is qualitatively different from that of carbon monoxide. Four probability maxima are found in this case, which are concentrated on regions along the bisector of each NP-Fe-NP quadrant. This conformation corresponds to the equilibrium structure of the Fe-02 bond. The small barrier among the minima (1.2 kcal/mol, as reported in the section, Static properties) is the reason for the lack of density in the direction along the Fe-NP bonds. In contrast, the high energy of a linear Fe-0-0, 15 kcal/mol (Rovira and Parrinello, 1999), precludes the sampling of this configuration at room temperature. The shape of the density pockets of Fig. 7 A reflects the frequent oscillations of the ligand within each quadrant, changing the Np-Fe01-02 torsional angle. This is consistent with the results of static calculations that show that the torsion around the Fe-O bond is a soft degree of freedom. To extract additional information on the 02 libration from the MD trajectory, the temporal Fourier transform of the velocity autocorrelation function for the iron and oxygen atoms was computed. The torsional mode corresponding to the 02 rotation around Fe-O is indeed characterized by a very low frequency (97 cm-'). The Fe-0-0 bending is found at 380 cm-'. To the best of our knowledge, this mode has not yet been assigned for oxymyoglobin, but it has been observed at 273 cm-' in heme models (Nakamoto, 1990). The 02 stretching frequency obtained (1180 cm- 1) is very close to the values reported for Mb02 (1103 cm-'; see Momenteau and Reed, 1994). The closest experimental realization of our model calculation is the picket-fence oxygen synthetic model (Jameson et al., 1978). It is therefore important to compare our results with the reported x-ray structure of the Fe-02 moiety: 0-0 = 1.15, 1.17 A, Fe-O = 1.75 A, <Fe-0-0 = 133, 129. These data are in apparent disagreement with our results: 0-0 = 1.30 A, Fe-O = 1.96 A, <Fe-0-0 = 1230, which are obtained by averaging these properties over our MD run. This could be attributed to the effect of the picket substituents, but our previous study on FeP(Im)02 and oxypicket fence (Rovira and Parrinello, 1999) showed these effects to be rather small, which rules out this possibility. However, we can reconcile theory and experiment if we recall that x-ray experiments do not measure distances and angles directly, but rather the positions of maximum probability, from which the other structural properties are deduced. We can prove this point from our trajectories, and, in fact, if we extract distances and angles from the position of maximum probability, we find 0-0 = 1. 19 A, Fe-O = 1.72 A, <Fe-0-0 = 1390, which is in much better agreement with experiment. Note that the experimentally reported 0-0 distances are very surprising because they are smaller than the reported gas phase value, which, for 02, is 1.23 A. Similar considerations hold for the reported data on the proteins, in which comparison with our results is further complicated by other affects, such as the presence of residues close to the heme pocket. In particular, the Fe-0-0 angles reported by x-ray and neutron structures of oxymyoglobin (1150) (Phillips, 1980; Phillips and Schoenborn, 1981) and oxyhemoglobin (1530 for the a subunit and 1590 for the 0 subunit) (Shaanan, 1983) are quite far from our average value (1230) and are not sampled in the simulation (Fig. 6).
In summary, our simulations of FeP(Im)(AB) (AB = CO, 02) reveal a picture of highly dynamic axial ligands. In the case of carbon monoxide, an essentially harmonic dynamics is found. The carbon monoxide ligand undergoes small, albeit extremely complex, displacements around its equilibrium position and its dynamics is not influenced by the imidazole ligand. The distributions obtained (Figs. 3, 4, and 7) represent the expected carbon monoxide dynamics in myoglobin in the absence of interaction with the polypeptide framework. This can be useful in the interpretation of the x-ray and spectroscopic measurements to determine the average Fe-CO structure, although, as mentioned before, care should be taken when associating a rigid structure with the highly dynamic Fe-CO moiety. In particular, the propensity for the oxygen to bend out from the porphyrin axial direction should be noted. Further interactions within the heme pocket could perturb the distributions reported here. For instance, a weak hydrogen bond (Unno et al., 1998) or an electrostatic interaction with His-64 would probably lead to the nonequivalence of the distribution of Fig. 7 A over the four porphyrin quadrants.
In the case of FeP(Im)(02), our simulation reveals a highly anharmonic dynamics for the 02 ligand, which undergoes large amplitude oscillations within one porphyrin quadrant and jumps from one to the other every 4-6 ps. This is consistent with the highly dynamic nature of 02 bound to heme proposed by several experiments in proteins and synthetic models (Jameson et al., 1978; Bowen et al., 1997; Spartalian et al., 1975; Mispelter et al., 1983; Oldfield et al., 1991) especially those that lack a hydrogen bond at the terminal oxygen. Ligand rotation in these models has been shown to occur by nuclear magnetic resonance experiments (Mispelter et al., 1983; Oldfield et al., 1991), on the basis of the equivalence of the pyrrole proton resonances. Our results suggest that, for a nonhydrogen bonded 02, precise determination of the rate of rotation would require picosecond time resolution.
In contrast, a possible hydrogen bond with His-64, which has been suggested several times as the origin of the discrimination between carbon monoxide and 0, would alter this picture. In this respect, restriction of the librational motion of the bound ligand caused by hydrogen bonding has been discussed in relation with the loss of entropy upon 02 binding to myoglobin (Filiaci and Nienhaus, 1997). Given the low frequency of the torsional mode of 02 rotation (97 cm^sup -1^), a weak hydrogen bond to His-64 (Phillips and Schoenborn, 1981; Shaanan, 1983) is indeed very likely to slow down the rotational motion of the ligand.
CONCLUSIONS
The room temperature motion of ligand binding to heme has been depicted by means of Car-Parrinello MD simulations on FeP(Im)(CO) and FeP(Im)(02) models. Our results illustrate the fluxionality of the Fe-CO and FC-02 bonds in the absence of the protein environment. From a technical point of view, they provide a reference that can be used to interpret future QM/MM calculations aimed at quantifying the role of the protein framework. The simulations reported here reflect a quite rigid Fe-CO bond, which undergoes little distortion around its equilibrium position. Rotation of the imidazole axial ligand around the Fe-N^sub epsilon^ bond is also observed, in agreement with experiments on heme models with imidazole-based axial ligands. Several features are shared with the analogous 02 model, but the bent Fe-02 bond shows a preference for a bisecting conformation, jumping over one Fe-NP bond toward a different porphyrin quadrant within 4-6 ps. Oscillations of the Fe-02 tilt and bend angles are quite large and, because of the anharmonicity of the Fe-02 motion, results obtained by an averaging value analysis might differ from those obtained from the maximum probability position. This reconciles the values reported in x-ray analysis with the average values we obtain in the dynamics. The rotational motion of the ligand is characterized by a frequency mode at 97 cm^sup -1^. Given this low value, the axial rotation of O2 would probably be slowed down by a weak hydrogen bond with His-64. Thus, in the case of Mb02 and a-Hb02 (Phillips and Schoenborn, 1981; Shaanan, 1983), only one of the quadrants would probably be selected.
We thank the Garching Computer Center (Garching, Germany) for computing support. C. Rovira acknowledges the financial support of the Training and Mobility of Researchers programme of the European Union under contract No. ERBFMBICT96-0951. We also thank S. Raugei, G. Lippert, R. Rousseau and E. Canadell for useful discussions.
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[Author Affiliation]
Carme Rovira and Michele Parrinello
Max-Planck Institut fur Festkorperforschung, Heisenbergstrasse 1, 70569 Stuttgart, Germany
[Author Affiliation]
Received for publication 20 April 1999 and in final form 20 October 1999.
Address reprint requests to Michele Parrinello, Max-Planck Institut fur Festkorperforschung, Heisenbergstrasse 1, 70569 Stuttgart, Germany. Tel.: +49-711-689-1700; Fax: +49-711-689-1702; E-mail: parrinello@prr.mpi. stuttgart.mpg.de.
[Author Affiliation]
Dr. Rovira's present address is Departament de Quimica Fisica, Universitat de Barcelona, Marti' i Franques 1, 08028 Barcelona, Spain.
(c)2000 by the Biophysical Society
The Holy Land's top Roman Catholic cleric assailed Israel's blockade of the Gaza Strip and urged Palestinians to heal their political rift in his first Christmas message on Tuesday.
Latin Patriarch Fouad Twal traveled to Gaza earlier this week to pray with the tiny Christian minority there, and used a news conference in Jerusalem on Tuesday to draw attention the plight of the territory's residents.
Just as Bethlehem, Jesus' traditional West Bank birthplace, waited for him, "so are we awaiting a manifestation of the Savior's grace that will put an end to the occupation and the injustice, delivering us from those fears, hardships and internal divisions that beset this land," Twal said.
The Jordanian-born cleric became the top Catholic leader in the Holy Land in June and is the second Palestinian to hold the post.
Israel has kept Gaza's borders nearly sealed since early November in response to frequent rocket fire by Gaza militants. This has led to shortages of many basic goods and twice forced the United Nations to suspend food aid distribution to the strip's neediest residents. Most now rely on goods smuggled in through tunnels under the Gaza-Egypt border.
Some 4,000 of the 1.4 million Gazans are Christian. About 600 are Roman Catholic.
Wearing a black robe and purple cap and flanked by other Catholic leaders, Twal called on the international community to reach a "just and final peace in the Holy Land," and encouraged Palestinians to seek political reconciliation.
Islamic Hamas militants violently seized control of Gaza in June 2007, creating dueling governments there and in the West Bank, which is ruled by Western-backed Palestinian President Mahmoud Abbas.
"We also call upon the Palestinians themselves to return to unity in the context of a recognized Palestinian legal structure, and in this way to spare the people the continuing and degrading siege," Twal said.
Recent attempts to reconcile Hamas and Abbas loyalists have failed.
Twal also expressed concern about the Holy Land's Christian communities, saying their presence is threatened by emigration and political instability.
The Palestinian Christian population in the Holy Land has fallen below 2 percent in the West Bank, Gaza and east Jerusalem _ down from an estimated 15 percent in 1950.
Twal also prayed for the people of Iraq, saying foreign military occupation had turned the country into "a jungle of chaos, violence and terrorism."
Iraqi Prime Minister Nouri al-Maliki on Tuesday ordered security officials to work for the release of a kidnapped Chaldean Catholic archbishop, calling Christians "an essential component of the Iraqi society."
Paulos Faraj Rahho was kidnapped and three of his companions were killed Friday when gunmen attacked them soon after he left Mass in the northern Iraqi city of Mosul, the latest in what church members called a series of attacks against Iraq's small Christian community.
Al-Maliki "has issued orders to the Interior Minister and the security officials in Nineveh province to meticulously follow this issue and work hard to release the archbishop as soon as possible," a statement by the prime minister's office said.
The U.S. military has said Iraqi and U.S. forces were searching for those who abducted the cleric. But Iraqi army Brig. Khalid Abdul-Sattar, the spokesman of the Nineveh province's joint operation command, said Tuesday that security forces in Mosul do not have any leads on Rahho's kidnapping.
"Christians in Iraq are an essential component of the Iraqi society and a part that cannot be separated from the Iraqi people and civilization. Any assault on the Christians is an assault on all Iraqis," the prime minister's statement said.
Pope Benedict XVI last week called for the swift release of Rahho, saying the "abominable" act was an attack on the Iraqi church as a whole. The European Union also has appealed for his release and condemned the kidnapping.
Chaldean Catholics comprise a tiny minority of the Iraqi population, but are the largest group among the less than 1 million Christians in predominantly Muslim Iraq. Since the U.S.-led invasion in 2003, Iraqi Christians have been targeted by extremists who label them "crusaders" loyal to U.S. troops.
Benedict has frequently expressed deep concern about the plight of Christians caught in the deadly sectarian crossfire in Iraq. Last fall, al-Maliki also pledged to protect and support the Christian minority.
Though most of Iraq has witnessed a decrease of violence over the past six months, the U.S. military regards Mosul as the last urban stronghold of al-Qaida in Iraq, and is engaged in a campaign with Iraqi forces to root out extremists from the city 225 miles northwest of Baghdad.
Police expressed concern today at the number of young driversacross Scotland who continue to run the risk of drinking anddriving.
In the two weeks since the festive campaign to crack down on drink and drug driving was launched, almost 150 drivers aged under25 have been caught over the limit.
The Association of Chief Police Officers in Scotland (ACPOS),which is backing the campaign, said the chances of drivers who hadtaken drink or drugs being caught was greater than ever.
Roadside testing is now carried out by police after all roadaccidents and suspected offences.
Chief Constable John Vine, chairman of ACPOS road policingbusiness area, said: "It is alarming that despite all our messageswarning of the dangers of driving while under the influence of drinkor drugs, young people in particular are failing to pay attention."
The anti-drink drive blitz is also to include adverts on thescreens of popular computer games, in a pilot project announcedtoday.
The adverts will be beamed directly into Xbox 360 games acrossScotland and will appear on billboards as young people play titles such as Need For Speed and Project Gotham Racing.
The Scottish Government is funding the pounds10,000 initiative.
Drew Miller scored his first career shootout goal in the eighth round and the Detroit Red Wings survived Minnesota's third-period rally to beat the Wild 4-3 on Thursday night.
Detroit goalie Jimmy Howard stopped six shots in the shootout and denied Eric Belanger in the eighth round to set up Miller's winner. Miller beat Niklas Backstrom, who entered the game after the first period in place of injured starter Josh Harding.
The Wild overcame a 3-1 deficit with third-period goals from Martin Havlat and Andrew Brunette.
Patrick Eaves gave the Red Wings a 2-1 advantage early in the third. Miller appeared to finish off the Wild when he took a pass from Derek Meech and made it 3-1 midway through the period, but the Wild continued their third-period success at home.
Havlat's unassisted goal at 13:48 held up after a review, and Brunette tied it a minute later, beating Jimmy Howard after controlling a bouncing puck.
Minnesota has outscored opponents 11-3 in the third in its last five home games.
Todd Bertuzzi also scored for Detroit.
Harding, Minnesota's backup , was making his first home start in over a year. He left with a lower-body injury after the first period and was replaced by Backstrom, the regular starter, to start the second.
Wild coach Todd Richards said he thought Harding injured his left hip early in the first while making two saves on a breakaway by Pavel Datsyuk and Eaves.
Backstrom, an All-Star last season, has struggled at times in Minnesota's new offensive-minded system. Backstrom had given up three goals or more in eight of his last 10 starts before Thursday.
Backstrom looked sharp to start the second and the Wild tied the game at 12:34 on fluky goal from Robbie Earl, who cleared waivers earlier this week but remains with the team. A shot from Shane Hnidy bounced off the side of the net, off the end boards, back over the net, and off of Earl's chest as he crashed the net.
The goal stood after a replay review to determine if the net became dislodged before the puck crossed the line.
Detroit continued a trend of jumping on the Wild in the first period. Bertuzzi forced Kim Johnsson to turn the puck over and scored on a breakaway 7:52 into the first.
The Wild have been outshot 51-16 in the first period of its last four games and have allowed the first goal in four straight.
Howard was back in goal for Detroit. The rookie had started 12 straight in place of veteran Chris Osgood before Osgood got the nod Tuesday night in a 3-2 loss at Washington.
Defenseman Brent Burns returned for the Wild after missing the last 29 games because of a concussion.
NOTES: Petr Sykora also cleared waivers for the Wild this earlier this week. The 33-year-old forward won't return to the team and the Wild will try to trade him. Sykora missed nearly two months with a concussion and had two goals and one assist in 14 games. ... Bertuzzi has scored against the Wild with four teams. ... Harding had stopped 73 of the last 75 shots he's faced before leaving. It was Backstrom's first relief appearance since Nov. 16, 2007, at Vancouver. ... Detroit is 4-5 in shootouts and Minnesota is 4-4.
Stocks gave up sizable gains Friday to fluctuate in the final hour of trading as Wall Street seemed likely to cap a big week quietly.
The Dow Jones industrial average had risen 150 points earlier in the session after Federal Reserve Chairman Ben Bernanke gave investors more reason to believe further interest rate cuts could be on the way. The tech-dominated Nasdaq composite index was lower after weak quarterly results from Dell Inc.
The market's fizzle Friday was perhaps to be expected following several sessions of sharp gains.
In a speech late Thursday, Bernanke said persistently tight credit conditions, the housing slump and high energy prices will probably create some "headwinds for the consumer in the months ahead," and the central bank will have to be "exceptionally alert and flexible."
The comments echoed those of Fed Vice Chairman Donald Kohn earlier in the week, which helped Wall Street recover some of its recent steep losses. Investors read Bernanke's words as a sign that the Fed is willing to lower interest rates again after cutting them at the past two meetings.
"Although the U.S. is in the eye of the credit storm, we've seen the Fed cut rates and we've heard from Bernanke that they're prepared to do so again if necessary," said Robert Jukes, global equity strategist at Collins Stewart in London.
The Fed meets again Dec. 11, and a rate cut could help reinvigorate the slowing economy. Evidence of a more reticent consumer came Thursday in a Commerce Department report that showed consumer spending rising a modest 0.2 percent in October, the slowest pace in four months.
The risk of rising inflation had been keeping the central bank cautious about loosening its policy. But that risk is looking less threatening now, given that oil prices have dipped below $90 a barrel for the first time since October and that the Commerce Department said core personal consumption expenditures have risen 1.9 percent year-over-year. Core PCE is one of the Fed's preferred inflation measures, and anything between 1 and 2 percent is considered a comfortable rate.
In late afternoon trading, the Dow rose 38.69, or 0.29 percent, to 13,350.42.
Broader stock indicators were mixed. The Standard & Poor's 500 index rose 8.42, or 0.57 percent, to 1,478.14, and the Nasdaq composite index fell 12.55, or 0.47 percent, to 2,655.58.
Advancing issues outnumbered decliners by more than 2 to 1 on the New York Stock Exchange, where volume came to 1.29 billion shares.
Government bonds fell as investors pulled their money out of the safe securities and put it back into stocks. The yield on the benchmark 10-year Treasury note, which moves opposite the price, rose to 3.96 percent from 3.94 percent late Thursday.
Crude oil prices fell $2.30 to settle at $88.71 per barrel _ their lowest levels in more than a month _ on the New York Mercantile Exchange.
The Dow is on pace to post its biggest weekly point gain since March 2003. After a sharp drop Monday that pulled the blue-chip index more than 10 percent below its record close, investors have piled on more than 600 points over the past four sessions. In addition to lifted chances for a rate cut, embattled financial companies like Citigroup Inc., Freddie Mac and E-Trade Financial Corp. announced strategies to raise cash _ building investors' confidence that credit problems may be on the mend.
However, the pace of the recovery _ and the remaining uncertainty about mortgages and credit availability _ raises questions about its sustainability. And despite the week's gains, stocks are poised to end November lower because of heavy declines amid worries about credit. The Dow began the session off 4.4 percent for November.
Gains in the technology sector are being limited by a murky outlook from Dell Inc., as well as by cautious comments on Research In Motion Ltd. from Piper Jaffray and a wary Goldman Sachs note on technology in general, according to Peter Boockvar, equity strategist at Miller Tabak.
The broader market is "being helped out by the hopes for a rates cut and the prospect of the government getting involved in fixing adjustable interest rates," he said.
Dell fell $3.93, or 14 percent, to $24.21, while Research In Motion fell $8.22, or 6.7 percent, to $113.86.
Other stocks that were the most actively traded and that showed the biggest gains on the New York Stock Exchange were ones that have been battered in recent months because of their link to mortgage troubles. The moves followed reports that the White House and major banks may be nearing a pact that would temporarily freeze interest rates on some subprime home loans, reducing the likelihood of default or foreclosure.
Countrywide Financial Corp. jumped $1.50, or 16.1 percent, to $10.80; Washington Mutual Inc. rose $1.43, or 7.9 percent, to $19.44; Freddie Mac rose $5.63, or 19.1 percent, to $35.14; and Citigroup Inc. rose $1.03, or 3.2 percent, to $33.32.
Other gainers were cell phone maker Motorola Inc. which said Edward J. Zander will step down as chief executive on Jan. 1 and President and Chief Operating Officer Greg Brown will take his place. Motorola has been trying to turn around its business amid falling sales and weak earnings. Its shares rose 21 cents to $15.86.
And Morgan Stanley rose 30 cents to $52.64, after ousting co-President Zoe Cruz late Thursday and moving co-President Robert Scully to the newly created Office of the Chairman.
The Russell 2000 index of smaller companies rose 5.29, or 0.69 percent, to 771.35.
The dollar was mixed against other major currencies, while gold prices fell.
Stocks gained overseas. Japan's Nikkei stock average rose 1.08 percent, and Hong Kong's Hang Seng index rose 0.57 percent. Britain's FTSE 100 rose 1.31 percent, Germany's DAX index rose 1.36 percent, and France's CAC-40 rose 1.29 percent.
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