text:
Bayern has to overcome 1-0 deficit against MadridThe Associated Press | April 29,2014FRANKFURT, Germany Bayern Munich has a chance to become the first club to win two straight titles since the Champions League formed in the 1992-93 season.
Bayern, however, is the only team to have conceded a goal in the first leg of the semifinals after losing to Real Madrid 1-0. Chelsea held on for a 0-0 draw at Atletico Madrid and will look to clinch its second final in three seasons at home Wednesday.
Here are some things to know ahead of the second-leg semifinals:
ATTACK MODE I: Real Madrid has honed its attack for the trip to Germany. Besides winning the Copa del Rey over Barcelona two weeks ago, Carlo Ancelottis side has stayed in the Spanish league title hunt by winning its last four games by the combined score of 17-0.
Cristiano Ronaldo scored his 46th and 47th goals of the season in all competitions on Saturday as Madrid crushed Osasuna 4-0, while also resting Gareth Bale as he recovers from the flu, striker Karim Benzema, defender Pepe and midfielder Xabi Alonso. Ancelotti said that Ronaldo is back to full fitness since a recent leg injury and that he expects both Bale and Benzema to play against Bayern Munich.
The Italian manager said he plans to go for the win instead of trying to make good on his teams slender 1-0 advantage. We want to score, not just defend, Ancelotti said. There is a good vibe in the team, a lot of confidence, and we are very motivated to play the match.
ATTACK MODE II: Bayern was also in scoring mode at home, when it put five past Werder Bremen in the Bundesliga. But it also conceded two and trailed twice after playing a very poor first half. Bayerns defense looked vulnerable against counterattacks precisely the way Madrid scored in the first leg.
Coach Pep Guardiola said the win was good for the mood before Tuesdays match, but did not hide his disappointment at how Bayern played in the first half.
Attacking midfielder Thomas Mueller was pragmatic. This game is not important but the mood is important and we need to make sure we release all our positive energy now, he said.
What should worry Bayern is its sudden weakness in defense it has conceded eight goals in its last three Bundesliga games at home.
BAYERN VS. REAL: Real Madrid has nine European Cup titles, while Bayern is a five-time champion. The two clubs with the most titles have met in European Cup semifinals five times, with Madrid coming through only once, in 2000. In the most recent tie, Bayern won on penalties in 2012.
Madrid knocked out German opposition, Schalke and Borussia Dortmund, in the previous rounds, but it has only two wins in Germany with 19 defeats and six draws. Bayern has eight wins against Madrid at home, with one draw.
CHELSEA AMBITION: The only trophy Jose Mourinho didnt collect in his first spell as Chelsea manager was the Champions League, and its the competition he wants to win at the end of his first season back. Not that there is much of a choice, as it still trails leader Liverpool by two points in the Premier League despite beating its rival 2-0 on Sunday.
Mourinho claims that finishing the season without a trophy wont trouble him.
When you give everything you have, when you try everything, when you work hard, when the group is good, when the group respects the club and the fans, you wait for the end of the season and you see what destiny has for you, Mourinho said.
Mourinho has long insisted this was a season of transition.
Frank Lampard and Jon Obi Mikel are suspended for the second leg, while first-choice goalkeeper Petr Cech has been ruled out after injuring his shoulder in Madrid. Mark Schwarzer, the 41-year-old Australian who protected the 0-0 draw in the first leg, is set to stay in goal for the home fixture.
He knows everything about the goal, about the small box, Mourinho said of Schwarzer. And when you are choosing a second goalkeeper you need to choose somebody that is especially mentally ready to play in any moment.
WINNING FORMULA: Atletico Madrids 1-0 win at Valencia on Sunday may have also served as a rehearsal for what it will hope to achieve at Stamford Bridge. Atletico continued its march toward the Spanish league title by again deploying a suffocating defense while getting the most out of its limited scoring chances. While a draw with goals will be enough to send it through to the final, Atletico will surely need to show the same poise at the back that it has demonstrated all season.
Atletico can also take heart that Chelsea has lost two of three European ties after drawing 0-0 away in the first leg.
We are competing at the highest level and we hope to take another step for us and the history of the club, said midfielder Raul Garcia, Atleticos scorer at Valencia. We will have to play our hearts out.MORE IN Wire SportsMEMPHIS, Tenn. Full StoryEAST RUTHERFORD, N.J. Full StoryLONDON Chelsea kept its three-point lead at the midpoint of the Premier League season Sunday... Full Story
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- RICHARD'S POOR ALMANACK: In 1900, a crew arrives at a Scottish isle lighthouse to find the previous crew has vanished; in 1944, George S. Patton relieves Bastogne; in 1890, 'Uncle Charlie' Osborne born; in 1891, Henry Miller born in New York.
- RICHARD'S POOR ALMANACK: Capt. James Cook discovers and names Christmas Island, Brits develop and test H-bombs there in 1957-58; 100 years ago today, Christmas truce takes hold on Western Front in France, combatants observe the holiday.
- RICHARD'S POOR ALMANACK: Gen. Wm. T. Sherman concludes March to the Sea, secures Savannah, Ga., offers the city as Christmas gift to Pres. Lincoln; N.Y.'s Lincoln Tunnel opens in 1937; first gorilla born in captivity, Colo, celebrates 58th birthday today.
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What was the initial purpose of creating this particular hybrid property type? Wasn't it to help the so-called "sandwich class"? But now as property developers of new executive condominiums (ECs) are creating options which are comparable to private properties, does it still serve its original purpose? Who are the ones actually benefiting from the EC scheme?
Forestville EC in Woodlands
First up, one does need to be reminded that land sold under the Government Land Sales programme are priced cheaper than those for private properties. Considering that permanent residents (PRs) are the most avid buyers of resale executive condominiums, are the eligibility criteria too lax thus pushing the prices up as both property buyers and developers alike recognise the hidden value of ECs? And with the narrowing of the price gap between ECs and private properties, will this instead nudge the price tag of the latter even higher?
If you compare a penthouse in an EC at $1.7 million to one in the private market at more that $3 million, which would you go for? The answer is clear. Should ECs have penthouse units or should they belong in the private market altogether. Do you think the government should step in to manage this sector as they did the Design Build and Sell Scheme (DBSS)?


text:
*sighs*I give up. --I feel like nothing I say and nothing I do is good enough. --I feel like Christina Maria Aguilera is good enough for anyone.--I feel that when someone meets the REAL me it's not good enough.--I feel that I'm starting to lose my friends.--I feel that I can only get attention of any kind if I'm taking off my clothes, singing, dancing, posing for a picture or complaining.--I feel like a bitch for posting this.I'm so sick of feeling this way. I'm a 22 year old woman with an amazing, if I do say so myself, career and loving friends and family. I should be happy. But, seriously, I'm feeling like shit. ... No one talks to me anymore unless I talk first. No one seems to care. Nothing. I'm feeling really lonely in the love department. ... I haven't had a boyfriend in..2 years or so..? I'm ready for a relationship. I've had my eye on pleanty of guys before but they're taken, not interested or gay. ... I really liked this one guy...but me and my stupid self didn't say anything when I had the chance. I said it way too late. I like this guy now but..he doesn't seem interested. .. I mean..what the hell is wrong with me!? .. Anyone wanna answer??*sighs* I'm just so tired of feeling this way.
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A visit to a city sky-high in the Andes is to step back into the 17th century and the tragedy that resulted from Spain's quest for wealth. Published August 24 2011
Northern European countries are going through growing pains acepting the concept of multi cultural societies. Many are fearful of what is known as the Islamization of Europe. Published August 10 2011
Commuting is not only hard on the wallet but on the environment and family life. Plus it can be a big waste of time. Published August 2 2011
Mario Salazar is a combat infantry Vietnam Vet, world traveler, renaissance reconnaissance man, pacifist, metal smith, glass artisan, computer programmer and he has a Master of Science in Civil/Environmental Engineering. Now retired from the Environmental Protection Agency and living ...Read More
Find up-to-date information on the D.C. and Baltimore live music scenes and read interviews with artists and reviews of the latest releases and concerts.
Florida singer/songwriter duo's recent performance at DC's 9:30 Club reviewed.
Bluegrass trio, The Devil Makes Three: Updated down-home action at the 9:30 Club.
Juliana Hatfield and Matthew Caws appearance as Minor Alps in DC.
Classic hardcore punks H2O in action in Silver Spring, Maryland.
Find the latest news and happening that effect those in the Washington D.C., Northern Virginia and Maryland Metro region.
All of the world's problems, solved on your back porch
A politically conservative and morally liberal Hebrew alpha male hunts left-wing viper
Television commentary, reviews, news and nonstop DVR catch-up by Lisa King Dolloff and friends.
The world of professional wrestling as seen through the eyes of columnist James Ryan, including previews, recaps, interviews and all of the latest wrestling news.


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Winsome Wood 92825 Wine Rack
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This Winsome Wood Wine Rack has a dark espresso finish.
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- Better Roads - http://www.betterroads.com -
New Ditch Witch JT100 Directional Drill Gives Power Where Power Is Due
Posted By admin On November 30, -0001 @ 12:00 am In Boomerang | No Comments
The Ditch Witch®organization announces the release of its most powerful directional drill, the JT100 Mach 1. Equipped with a 268-hp (200 kW) engine, the JT100 is designed so that rotation, thrust, and drilling fluid flow can operate simultaneously at full power, which leads to faster job completion.
To find out more about the new Ditch Witch JT100, please visit the Ditch Witch Press Center, where you can download press releases and high-res photography. If you need anything, just send me an e-mail. Thank you for your continued support of Ditch Witch products.
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text: Ok, about a month ago i bought two Fire Belly Toads, thinking they were both male. Their names are Kermit and Hercules. Kermit looks a little smaller than Hercules, but he also seems rounder than Hercules. In fact, Kermit has been shedding, but Hercules hasn't. Is it because Kermit is growing, growing from pregnancy, or is it that Hercules is older than Kermit? About two weeks ago I saw Hercules on top of Kermit, and I'm sure it wasn't a "Toad pile" because Hercules was embracing Kermit, and Kermit was not trying to get away, and he wasn't swimming around. Hercules (on top) wasn't barking or anything, but it sounded like Kermit was making a chirping sound... I think it might have been the un-mounting call? Now for about a week, maybe a week an a half, Kermit and Hercules have always hung around in a specific corner of their tank (in the water). Kermit it always first in the corner, and Hercules is right behind him, as if he is "guarding" Kermit. Hercules always has his hands on Kermit's back when they are in the corner. Kermit doesn't seem to care. Since i saw them possibly mating, I have't seen them do it again. If Kermit does end up laying 200 eggs, what do I do with all of them? I don't want to spend a bunch of time trying to sell them. I MIGHT possibly want to keep one or two of them. I'm afraid that if I take the eggs to a lake they'll get eaten or something. Does anyone know what's going on? Thanks for your help!


text:
The Furniture +Plus
by oskarcio -
Minecraft: 1.4.7
Platform URL
This pack contains:
Redpower(all of the jars)
Repower 2
Jammy's furniture mod
1.0-Added the Modpack to Technic
The rights for creating this modpack goes to me.
The rights for the mods go to their respectful owners.
In no way did i create the mods that are in this modpack,if the authors ask me to remove this i will.
Created: 05-31-2013
Last Updated: 1 year ago


text:
BEDFORD TOWNSHIP — A home invasion was discovered shortly after noon Wednesday in the 15000 block of Poplar Dr., the Monroe County Sheriff's Office reported.
The stolen items included a television, a small safe and prescription medication.
Two bicycles were left at the scene.
K9 unit was called to help with the search, but the suspects were not located.
Michigan State Police assisted at the scene.
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Book your room at La Quinta Inn Everett
Standard Room, 2 Queen BedsMax Occupancy: 4 guests (up to 3 children, 3 infants)
King with microwave & fridgeMax Occupancy: 3 guests (up to 2 children, 1 infant)
Everett hotel with an outdoor pool
Situated in Everett, this hotel is close to Everett Mall. Area attractions also include Boeing Everett Factory and Harbour Pointe Golf Club.
Hotel Features
In addition to complimentary wireless Internet access, La Quinta Inn Everett provides a 24-hour business center, complimentary high-speed (wired) Internet access, and free self parking.
Room Amenities
Televisions come with cable channels. Guestrooms also feature complimentary wireless Internet access, complimentary high-speed (wired) Internet access, and air conditioning.Information missing or incorrect? Tell us!
At your hotel
At your hotel
High-speed wired and wireless Internet access is complimentary. This hotel offers access to a 24-hour business center and a meeting room. A complimentary breakfast is offered. Event facilities measure 400 square feet (36 square meters). This Everett hotel also offers an outdoor pool, coffee/tea in the lobby, and complimentary newspapers in the lobby. Onsite self parking is complimentary.
La Quinta Inn Everett is a smoke-free property.
- Conference space size (feet) - 400
- Conference space size (meters) - 36
- One meeting room
- Number of buildings/towers - 1
- 24-hour front desk
- Number of floors - 3
- Smoke-free property
- Coffee/tea in lobby
- Complimentary newspapers in lobby
- Express check-out
- Elevator/lift
- Express check-in
- Fireplace in lobby
- Outdoor pool
- Total number of rooms - 73
- 24-hour business center
- Free self parking
- Television in lobby
- Free breakfast
- Free Wi-Fi
- Free wired high-speed Internet
Stay connected
Available in all rooms: Free Wi-Fi , Free wired high-speed Internet
Available in some public areas: Free Wi-Fi , Free wired high-speed Internet
Park your car
Free self parking
In your room
- Air conditioning
- Phone
- Cable TV service
- Coffee/tea maker
- Complimentary newspaper
- Complimentary toiletries
- Free local calls
- Hair dryer
- Daily housekeeping
- Iron/ironing board
- Climate control
- Premium bedding
- Separate sitting area
- Shower/tub combination
- Free Wi-Fi
- Free wired high-speed Internet
Eat and drink
Guests are offered a complimentary continental breakfast.
The recreational activities listed below are available either on site or nearby; fees may apply.
- Golfing nearby
- Hiking/biking trails nearby
- Mountain biking nearby
To make requests for specific accessibility needs, complete the "Special or Accessibility Requests" section of "Trip Preferences" when you book your hotel.
- Accessible bathroom
- Accessible parking
The fine print for La Quinta Inn Everett
When you arrive
Check-in time starts at 3 PM
When you leave
Check-out time is 11 AM
How you can pay
Your pets
Pets allowed
You need to know
Extra-person charges may apply and vary depending on hotel policy.
Government-issued photo identification and a credit card are required at check-in for incidental charges.
Special requests are subject to availability upon check-in and may incur additional charges. Special requests cannot be guaranteed.


text:
« Album Cover: Fantasia – 'Side Effects of You'
Wiz Khalifa and Amber Rose Welcome Son Sebastian 'The Bash' Taylor Thomaz »
New Music: Mike Posner f/ Blackbear – 'OshFest'
Mike Posner takes a trip back in time on his laid-back jam "OshFest" featuring punk rocker Blackbear. Following his posse remix to Drake's "Started From the Bottom," the Detroit singer reminisces on being a college kid making beats in his dorm, never imagining he would one day become a star.
"Every summer my best friends and I migrate back to Northern Michigan and spend a weekend at my homie's Osh's crib," said Posner. "For three days I'm surrounded by the people that will love me no matter what. Enjoy this song with your crew."
He had plans to include the song on his upcoming album. "I was gonna save this song for my album but you deserve it now," he wrote.
Kick back and share in Posner's passion for life.
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WELCOME | January | February | March | April | May | June | July | August | September | October | November | December | Index
Please feel free to use these exercises for your writing group or classroom; however, for permission to reprint on-line, in a magazine, book, or other format, please contact the author for permission.
From October
1, 2005- September 30, 2006 I posted a daily 5 minute writing exercise
addressing aspects of craft as varied as point of view, dialogue,
plot, synthesthesia, body language, imagery, and beginnings.
Most of the exercises are mine, but several are from other poets
and writers, as you will see. "Giant Golden Buddha" and the other
364 are now posted here. May they be both fun and useful for
your writing.


text:
Another day, another story,
Thursday, August 12, 2010
The Facts of Life
Number 3 to Number 4, in the car today, "If you don't buckle your seat you will fly through the window and be killed and then Mom will get pregnant again and we'll have to get a new baby and name him your name."
Another day, another story,
Another day, another story,
Posted by Emily T. Thomas at 12:36 PM
2 comments:
- Em and Lib said...
Love his logic!!
- August 12, 2010 at 1:20 PM
- magsmcc said...
Oh my word- I am laughing so hard I have tears in my eyes- all because the sheer clever cruelty of this is becoming part of the tapestry of my daily existence!
- August 16, 2010 at 3:57 AM
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Outsourcing Guide
Cont. Education
Training Courses
Web Seminars
Buyer's Guide
Home Page
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Pharm News
Federal Register
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FDA Links
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Pharm/Biotech Events
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Protection of cardiac myocardium
United States Patent: 7,504,379
Issued: March 17, 2009
Inventors: Edelberg; Jay
(New York, NY), Xaymardan; Munira (Toronto, CA)
Assignee: Cornell Research
Foundation, Inc. (Ithaca, NY)
Appl. No.: 11/129,076
Filed: May 13, 2005
Web Seminars -- Pharm/Biotech/etc.
The invention provides compositions and
methods for protecting vascular tissues from injury that occurs, for
example, during occlusion of one or more arteries. In some embodiments,
the injury is myocardial infarction. The compositions of the invention
include combinations of platelet derived growth factor, vascular
endothelial growth factor, and angiopoietin-2.
Description of the
The invention provides compositions and methods for protecting vascular
tissue in a patient from damage, for example, during occlusion of an artery.
In some embodiments, the compositions and methods are used to prevent or
treat tissue injuries resulting from myocardial infarction.
The methods of the invention involve administering to the patient a
composition comprising a therapeutically effective amount of
platelet-derived growth factor, angiopoietin-2, and vascular endothelial
growth factor. The composition can also include a pharmaceutically
acceptable carrier.
In one embodiment, the invention provides a method of promoting vascular
health in a patient by administering to the patient a therapeutically
effective amount of platelet derived growth factor, angiopoietin-2, and
vascular endothelial growth factor.
In another embodiment, the invention provides a method of protecting cardiac
tissue in a patient from damage during myocardial infarction by
administering to the patient a therapeutically effective amount of platelet
derived growth factor, angiopoietin-2, and vascular endothelial growth
In yet another embodiment, the invention provides a method of improving
survival of transplanted tissue in a patient by administering to the patient
a therapeutically effective amount of platelet derived growth factor,
angiopoietin-2, and vascular endothelial growth factor.
Administration can be parenteral, as by intravascular, intravenous,
intraarterial, intraperitoneal, intraventricular infusion, stent, infusion
catheter, balloon catheter, bolus injection, topical administration as by
direct application to tissue surfaces during surgery, or oral.
Alternatively, administration can be directly into the heart or into the
vasculature of the patient.
The platelet-derived growth factor employed can, for example, be platelet
derived growth factor AB, platelet derived growth factor A, platelet derived
growth factor B, or mixtures thereof. In some embodiments, the
platelet-derived growth factor can have a sequence comprising SEQ ID NO:1,
SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6 or a mixture
thereof. The angiopoietin-2 can, for example, have a sequence comprising SEQ
ID NO:7, SEQ ID NO:8, or a mixture thereof. The vascular endothelial growth
factor can, for example, have a sequence comprising SEQ ID NO:9, SEQ ID
NO:10, SEQ ID NO:11, SEQ ID NO:12 or a mixture thereof.
The size of necrosis, vascular injury or myocardial infarction in the
patient can be reduced by such compositions and methods of the invention.
The present invention provides pharmaceutical compositions comprising an
effective amount of platelet-derived growth factor (PDGF), angiopoietin-2
(Ang-2) and vascular endothelial growth factor (VEGF) that are effective for
preventing damage to cardiac tissues as a result of vascular conditions or
diseases, for example, those conditions and diseases that can lead to
occlusion of an artery. Such administration is given before, during or as
soon as possible after arterial occlusion.
Vascular Diseases
The vascular diseases treated by the present invention are vascular diseases
of mammals. The word mammal means any mammal. Some examples of mammals
include, for example, pet animals, such as dogs and cats; farm animals, such
as pigs, cattle, sheep, and goats; laboratory animals, such as mice and
rats; primates, such as monkeys, apes, and chimpanzees; and humans.
According to the invention, endothelial cells within normal vascular tissues
change as they grow older, exhibiting reduced angiogenesis and losing their
ability to communicate with other cells by secreting signaling agents. These
changes can lead to a diminished capacity for blood vessel formation, a
reduction in blood flow to the associated organ or system, and an inability
to recover from injuries or diseases that can block or adversely affect
blood vessels.
Many pathological conditions can lead to vascular diseases that can block
blood vessels such as atherosclerosis, preeclampsia, peripheral vascular
disease, erectile dysfunction, cancers, renal failure, heart disease, and
stroke. Such conditions are associated with alterations in the normal
vascular condition of the affected tissues and/or systems.
Accordingly, this invention relates to methods for treating endothelial
dysfunction, such as a vascular condition or a circulatory condition
associated with loss, injury or disruption of the vasculature within an
anatomical site or system. The term "vascular condition" or "vascular
disease" refers to a state of vascular tissue where blood flow is, or can
become, impaired or even blocked.
Examples of vascular conditions or vascular disease to which the methods of
the invention apply are those in which the vasculature of the affected
tissue or system is injured, senescent, or otherwise altered in some way, so
that blood flow to the tissue or system is reduced or is in danger of being
reduced. Vascular, circulatory or hypoxic conditions to which the methods of
the invention apply are those associated with, but not limited to,
myocardial infarction, maternal hypoxia (e.g., placental hypoxia,
preeclampsia), abnormal pregnancy, peripheral vascular disease (e.g.,
arteriosclerosis), transplant accelerated arteriosclerosis, deep vein
thrombosis, erectile dysfunction, cancers, renal failure, stroke, heart
disease, sleep apnea, hypoxia during sleep, female sexual dysfunction, fetal
hypoxia, respiratory disorders due to smoking, anemia, hypovolemia, vascular
or circulatory conditions which increase risk of metastasis or tumor
progression, hemorrhage, hypertension, diabetes, vasculopathologies,
disorders due to surgery (e.g., per-surgical hypoxia, post-operative
hypoxia), Raynaud's disease, endothelial dysfunction, regional perfusion
deficits (e.g., limb, gut, renal ischemia), stroke, thrombosis, frost bite,
decubitus ulcers, asphyxiation, poisoning (e.g., carbon monoxide, heavy
metal), altitude sickness, pulmonary hypertension, sudden infant death
syndrome (SIDS), asthma, chronic obstructive pulmonary disease (COPD),
congenital circulatory abnormalities (e.g., Tetralogy of Fallot) and
erythroblastosis (blue baby syndrome). In particular embodiments, the
invention provides methods of treating loss of circulation or endothelial
dysfunction in a mammal such as a human patient.
Thus, the invention is directed to methods of promoting vascular health by
preventing or treating diseases or conditions like those listed above. In
some embodiments, the disease or condition is stroke, atherosclerosis, acute
coronary syndromes including unstable angina, thrombosis and myocardial
infarction, plaque rupture, both primary and secondary (in-stent) restenosis
in coronary or peripheral arteries, transplantation-induced sclerosis,
peripheral limb disease, intermittent claudication and diabetic
complications (including ischemic heart disease, peripheral artery disease,
congestive heart failure, retinopathy, neuropathy and nephropathy), or
In some embodiments, the vascular condition or vascular disease arises from
injured or damaged myocardium. As used herein injured or damaged myocardium
refers to myocardial cells that have been exposed to ischemic conditions.
These ischemic conditions may be caused by a myocardial infarction,
transplant injury, heart surgery or cardiovascular disease. The lack of
oxygen causes the death of the cells in the surrounding area, leaving an
infarct that can eventually scar.
Preferably, injured or damaged myocardium is treated with the methods and
compositions of the invention before damage occurs (e.g. when damage is
suspected of occurring or a possibility exists of potential vascular
injury), during injury or as quickly as possible after injury or damage
occurs. Hence, the methods and compositions of the invention are
advantageously employed on tissues that may be experiencing, are
experiencing, have just experienced or are in danger of ischemia, myocardial
infarction, heart attack or loss of blood flow. The methods and compositions
of the invention are also advantageously employed on recently damaged
vascular tissues (e.g. myocardium) and on not so recently damaged vascular
tissues (e.g. myocardium).
As used herein "recently damaged vascular tissues" refers to vascular
tissues (or myocardium) that has been damaged within zero to one day of
treatment being started. In a preferred embodiment, the tissue (or
myocardium) has been damaged within zero to twelve hours of the start of
treatment. In a further preferred embodiment, the tissue or myocardium has
been damaged within 6 hours of the start of treatment.
The methods and compositions of the invention can be used to prevent or to
treat vascular conditions such as those listed above. These methods involve
administering an effective amount of a combination of platelet-derived
growth factor (PDGF), angiopoietin-2 (Ang-2) and vascular endothelial growth
factor (VEGF). Such an effective amount is effective when it reduces the
extent of damage due to vascular injury, vascular occlusion or myocardial
Platelet-Derived Growth Factor
Naturally occurring, platelet-derived growth factor ("PDGF") is a
disulfide-bonded dimer having two polypeptide chains, namely the "A" and "B"
chains, with the A chain being approximately 60% homologous to the B chain.
Naturally occurring PDGF is found in three dimeric forms, namely PDGF-AB
heterodimer, PDGF-BB homodimer, or PDGF-AA homodimer. Hannink et al., Mol.
Cell. Biol., 6, 1304-1314 (1986). PDGF-AB has been identified as the
predominant naturally occurring form. However, some data indicates that the
PDGF-BB homodimer may be effective for wound healing. Each monomeric subunit
of the biologically active dimer, irrespective of whether it is an A chain
monomer or a B chain monomer, contains eight cysteine residues. Some of
these cysteine residues form interchain disulfide bonds that hold the dimer
together. As used herein, the term PDGF means any PDGF polypeptide or
protein, including PDGF A, PDGF B, PDGF AB, PDGF BB, and PDGF AA.
The A polypeptide of human PDGF can be any mammalian PDGF A polypeptide
including, for example, human, mouse, rat, rabbit, goat, bovine, horse,
sheep and any other mammalian PDGF A polypeptide. The following sequence is
one example of an amino acid sequence of a human PDGF A polypeptide (SEQ ID
-- see Original Patent.
The following sequence is an
example of a mouse PDGF A sequence (SEQ ID NO:2)
-- see Original Patent.
Other sequences for PDGF A can readily be obtained by one of skill in the
art, for example, from the GenBank database of sequences. Variability in
these and other sequences is permitted so long as the PDGF A polypeptide can
dimerize with PDGF B and/or function in cell-to-cell communication.
The PDGF B polypeptide found in human platelets has been identified as a 109
amino acid cleavage product (PDGF-B.sub.109) of a 241 amino acid precursor
polypeptide Johnsson et al., EMBO Journal, 3(5), 921-928 (1984). An example
of a human sequence for the PDGF B polypeptide is provided below (SEQ ID
-- see Original Patent.
The following sequence is an example of a mouse PDGF B sequence (SEQ ID
-- see Original Patent.
A 109 amino acid PDGF B polypeptide is believed to be the mature form of
PDGF in humans and constitutes a cleavage product of the PDGF-B precursor
protein. Homology with the precursor protein begins at amino acid 82 of the
241 amino acid precursor protein and continues for 109 amino acids yielding,
for example, a polypeptide with the following sequence (SEQ ID NO:5)
-- see Original Patent.
Another form of PDGF-B
(PDGF-B.sub.119), corresponds to the first 119 amino acids of the PDGF-B
precursor protein (SEQ ID NO:6)
-- see Original Patent.
This PDGF-B.sub.119 form has
also been identified as a major cleavage product of the precursor protein
when the entire gene is expressed in a transfected mammalian host. See U.S.
Pat. No. 5,149,792.
Human platelet-derived growth factor is believed to be the major mitogenic
growth factor in serum for connective tissue cells. PDGF can positively
affect mitogenesis in arterial smooth muscle cells, fibroblast cells lines,
and glial cells. Deuel et al., J. Biol. Chem., 256(17), 8896-8899 (1981).
See also, e.g., Heldin et al., J. Cell Physiol., 105, 235 (1980) (brain
glial cells); Raines and Ross, J. Biol. Chem., 257, 5154 (1982) (monkey
arterial smooth muscle cells). PDGF is also believed to be a chemoattractant
for fibroblasts, smooth muscle cells, monocytes, and granulocytes.
An angiogenic factor, which was originally called TIE-2 ligand-1 (TL1), but
which is also referred to as angiopoietin-1 (Ang1) is required for normal
vascular development in the mouse. Angiopoietin-2 (also called TIE-2
ligand-2, TL2) is believed to be a naturally occurring antagonist for Ang1
and the angiopoietin-2 receptor. A description of the cloning and sequencing
of TL1 (Ang1) and TL2 (Ang2) as well as for methods of making and uses
thereof is provided in PCT International Publication No. WO 96/11269
published Apr. 18, 1996, PCT International Publication No. WO 96/31598
published Oct. 10, 1996 and S. Davis, et al., Cell 87: 1161-1169 (1996) each
of which is hereby incorporated by reference.
One example of a sequence of a human angiopoietin-2 precursor polypeptide is
as follows (SEQ ID NO:7)
-- see Original Patent.
Another example of a sequence of a human angiopoietin-2 precursor
polypeptide is as follows (SEQ ID NO:8)
-- see Original Patent.
Vascular Endothelial Growth
Vascular endothelial growth factor (VEGF) (Ferrara et al., Endo. Rev., 13:
18-32 [1992]) is a potent angiogenic factor that acts via the endothelial
cell-specific receptor tyrosine kinases fins-like tyrosine kinase (Flt1) and
fetal liver kinase (Flk1) (also designated KDR). Shibuya et al., Oncogene,
5: 519-524 (1990); Devries et al., Science, 255: 989-991 (1992); Quinn et
al., Proc. Natl. Acad. Sci. USA, 90: 7533-7537 (1993); Millauer et al.,
Cell, 72: 835-846 (1993); Matthews et al., Proc. Natl. Acad. Sci. USA, 88:
9026-9030 (1991); Terman et al., Biochem. Biophys. Res. Commun., 187:
1579-1586 (1992); Terman et al., Oncogene, 6: 1677-1683 (1991); Oelrichs et
al., Oncogene, 8: 11-18 (1993). These two VEGF receptors and a third orphan
receptor, Flt4 (Pajusola et al., Cancer Res., 52: 5738-5743 [1992]; Galland
et al., Oncogene, 8: 1233-1240 [1993]; Finnerty et al., Oncogene, 8:
2293-2298 [1993]) constitute a subfamily of class III receptor tyrosine
kinases that contain seven extracellular immunoglobulin-like domains and a
split intracellular tyrosine kinase domain. Mustonen and Alitalo, J. Cell.
Biol., 129: 895-898 (1995). See also WO 94/10202 published May 11, 1994 and
PCT/US93/00586 filed Jan. 22, 1993 (Avraham et al.). These three receptors
have 31-36% amino acid identity in their extracellular ligand-binding
VEGF is a homodimeric, cysteine-rich protein that can occur in at least four
forms due to alternative splicing of its mRNA. Ferrara et al., Endo. Rev.,
13: 18-32 [1992]). One example of a VEGF polypeptide that may be used in the
invention is a polypeptide of the following sequence (SEQ ID NO:9)
-- see Original Patent.
Another example of a VEGF polypeptide that may be used in the invention is
vascular endothelial growth factor B precursor, which has the following
sequence (SEQ ID NO:10)
-- see Original Patent.
Another example of a VEGF
polypeptide that may be used in the invention is vascular endothelial growth
factor C preproprotein, which has the following sequence (SEQ ID NO:11)
-- see Original Patent.
Another example of a VEGF polypeptide that may be used in the invention is
vascular endothelial growth factor D precursor, which has the following
sequence (SEQ ID NO:12)
-- see Original Patent.
As recognized by one of skill in the art, each of the PDGF, angiopoietin-2
and VEGF polypeptides from different mammalian species have similar amino
acid sequences. According to the invention any PDGF, angiopoietin-2 and VEGF
polypeptide from any mammalian species can be utilized in the practice of
the invention so long as the PDGF, angiopoietin-2 and VEGF polypeptide can
stimulate endothelial cells to promote angiogenesis.
The polypeptides of the invention, including their salts, are preferably
administered so as to achieve a reduction in at least one symptom associated
with a myocardial infarction, or a decrease in the degree or amount of
tissue injury associated with myocardial infarction or heart attack.
To achieve the desired effect(s), the polypeptides or variants thereof, may
be administered as single or divided dosages, for example, of at least about
0.01 mg/kg to about 500 to 750 mg/kg, of at least about 0.01 mg/kg to about
300 to 500 mg/kg, at least about 0.1 mg/kg to about 100 to 300 mg/kg or at
least about 1 mg/kg to about 50 to 100 mg/kg of body weight, although other
dosages may provide beneficial results. The amount administered will vary
depending on various factors including, but not limited to, the polypeptides
chosen, the disease, the weight, the physical condition, the health, the age
of the mammal, whether prevention or treatment is to be achieved, and if the
peptide is chemically modified. Such factors can be readily determined by
the clinician employing animal models or other test systems that are
available in the art.
Administration of the combination of therapeutic agents in accordance with
the present invention may be in a single dose, in multiple doses, in a
continuous or intermittent manner, depending, for example, upon the
recipient's physiological condition, whether the purpose of the
administration is therapeutic or prophylactic, and other factors known to
skilled practitioners. The administration of the polypeptides of the
invention may be essentially continuous over a pre-selected period of time
or may be in a series of spaced doses. Both local and systemic
administration is contemplated.
To prepare the composition, polypeptides are synthesized or otherwise
obtained, purified as necessary or desired and then lyophilized and
stabilized. A given polypeptide can then be adjusted to the appropriate
concentration, and optionally combined with other agents. The absolute
weight of a given polypeptide included in a unit dose can vary widely. For
example, about 0.01 to about 2 g, or about 0.1 to about 500 mg, of the
combination of polypeptides of the invention. Alternatively, the unit dosage
can vary from about 0.01 g to about 50 g, from about 0.01 g to about 35 g,
from about 0.1 g to about 25 g, from about 0.5 g to about 12 g, from about
0.5 g to about 8 g, from about 0.5 g to about 4 g, or from about 0.5 g to
about 2 g.
Daily doses of the polypeptide combination of the invention can vary as
well. Such daily doses can range, for example, from about 0.1 g/day to about
50 g/day, from about 0.1 g/day to about 25 g/day, from about 0.1 g/day to
about 12 g/day, from about 0.5 g/day to about 8 g/day, from about 0.5 g/day
to about 4 g/day, and from about 0.5 g/day to about 2 g/day.
Thus, one or more suitable unit dosage forms comprising the therapeutic
polypeptides of the invention can be administered by a variety of routes
including oral, parenteral (including subcutaneous, intravenous,
intramuscular and intraperitoneal), rectal, dermal, transdermal,
intrathoracic, intrapulmonary and intranasal (respiratory) routes. The
therapeutic polypeptides may also be formulated for sustained release (for
example, using microencapsulation, see WO 94/07529, and U.S. Pat. No.
4,962,091). The formulations may, where appropriate, be conveniently
presented in discrete unit dosage forms and may be prepared by any of the
methods well known to the pharmaceutical arts. Such methods may include the
step of mixing the therapeutic agent with liquid carriers, solid matrices,
semi-solid carriers, finely divided solid carriers or combinations thereof,
and then, if necessary, introducing or shaping the product into the desired
delivery system.
When the therapeutic polypeptides of the invention are prepared for oral
administration, they are generally combined with a pharmaceutically
acceptable carrier, diluent or excipient to form a pharmaceutical
formulation, or unit dosage form. For oral administration, the polypeptides
may be present as a powder, a granular formulation, a solution, a
suspension, an emulsion or in a natural or synthetic polymer or resin for
ingestion of the active ingredients from a chewing gum. The active
polypeptides may also be presented as a bolus, electuary or paste. Orally
administered therapeutic polypeptides of the invention can also be
formulated for sustained release, e.g., the polypeptides can be coated,
micro-encapsulated, or otherwise placed within a sustained delivery device.
The total active ingredients in such formulations comprise from 0.1 to 99.9%
by weight of the formulation.
By "pharmaceutically acceptable" it is meant a carrier, diluent, excipient,
and/or salt that is compatible with the other ingredients of the
formulation, and not deleterious to the recipient thereof.
Pharmaceutical formulations containing the therapeutic polypeptides of the
invention can be prepared by procedures known in the art using well-known
and readily available ingredients. For example, the polypeptide can be
formulated with common excipients, diluents, or carriers, and formed into
tablets, capsules, solutions, suspensions, powders, aerosols and the like.
Examples of excipients, diluents, and carriers that are suitable for such
formulations include buffers, as well as fillers and extenders such as
starch, cellulose, sugars, mannitol, and silicic derivatives. Binding agents
can also be included such as carboxymethyl cellulose, hydroxymethylcellulose,
hydroxypropyl methylcellulose and other cellulose derivatives, alginates,
gelatin, and polyvinyl-pyrrolidone. Moisturizing agents can be included such
as glycerol, disintegrating agents such as calcium carbonate and sodium
bicarbonate. Agents for retarding dissolution can also be included such as
paraffin. Resorption accelerators such as quaternary ammonium compounds can
also be included. Surface-active agents such as cetyl alcohol and glycerol
monostearate can be included. Adsorptive carriers such as kaolin and
bentonite can be added. Lubricants such as talc, calcium and magnesium
stearate, and solid polyethyl glycols can also be included. Preservatives
may also be added. The compositions of the invention can also contain
thickening agents such as cellulose and/or cellulose derivatives. They may
also contain gums such as xanthan, guar or carbo gum or gum arabic, or
alternatively polyethylene glycols, bentones and montmorillonites, and the
For example, tablets or caplets containing the polypeptides of the invention
can include buffering agents such as calcium carbonate, magnesium oxide and
magnesium carbonate. Caplets and tablets can also include inactive
ingredients such as cellulose, pre-gelatinized starch, silicon dioxide,
hydroxy propyl methyl cellulose, magnesium stearate, microcrystalline
cellulose, starch, talc, titanium dioxide, benzoic acid, citric acid, corn
starch, mineral oil, polypropylene glycol, sodium phosphate, zinc stearate,
and the like. Hard or soft gelatin capsules containing at least one
polypeptide of the invention can contain inactive ingredients such as
gelatin, microcrystalline cellulose, sodium lauryl sulfate, starch, talc,
and titanium dioxide, and the like, as well as liquid vehicles such as
polyethylene glycols (PEGs) and vegetable oil. Moreover, enteric-coated
caplets or tablets containing one or more polypeptides of the invention are
designed to resist disintegration in the stomach and dissolve in the more
neutral to alkaline environment of the duodenum.
The therapeutic polypeptides of the invention can also be formulated as
elixirs or solutions for convenient oral administration or as solutions
appropriate for parenteral administration, for instance by intramuscular,
subcutaneous, intraperitoneal or intravenous routes. The pharmaceutical
formulations of the therapeutic polypeptides of the invention can also take
the form of an aqueous or anhydrous solution or dispersion, or alternatively
the form of an emulsion or suspension or salve.
Thus, the therapeutic polypeptides may be formulated for parenteral
administration (e.g., by injection, for example, bolus injection or
continuous infusion) and may be presented in unit dose form in ampoules,
pre-filled syringes, small volume infusion containers or in multi-dose
containers. As noted above, preservatives can be added to help maintain the
shelve life of the dosage form. The active polypeptides and other
ingredients may form suspensions, solutions, or emulsions in oily or aqueous
vehicles, and may contain formulatory agents such as suspending, stabilizing
and/or dispersing agents. Alternatively, the active polypeptides and other
ingredients may be in powder form, obtained by aseptic isolation of sterile
solid or by lyophilization from solution, for constitution with a suitable
vehicle, e.g., sterile, pyrogen-free water, before use.
These formulations can contain pharmaceutically acceptable carriers,
vehicles and adjuvants that are well known in the art. It is possible, for
example, to prepare solutions using one or more organic solvent(s) that
is/are acceptable from the physiological standpoint, chosen, in addition to
water, from solvents such as acetone, ethanol, isopropyl alcohol, glycol
ethers such as the products sold under the name "Dowanol," polyglycols and
polyethylene glycols, C.sub.1-C.sub.4 alkyl esters of short-chain acids,
ethyl or isopropyl lactate, fatty acid triglycerides such as the products
marketed under the name "Miglyol," isopropyl myristate, animal, mineral and
vegetable oils and polysiloxanes.
It is possible to add, if necessary, an adjuvant chosen from antioxidants,
surfactants, other preservatives, film forming, keratolytic or comedolytic
agents, perfumes, flavorings and colorings. Antioxidants such as t-butylhydroquinone,
butylated hydroxyanisole, butylated hydroxytoluene and .alpha.-tocopherol
and its derivatives can be added.
Also contemplated are combination products that include one or more
polypeptides of the present invention and one or more other anti-microbial
agents. For example, a variety of antibiotics can be included in the
pharmaceutical compositions of the invention, such as aminoglycosides (e.g.,
streptomycin, gentamicin, sisomicin, tobramycin and amicacin), ansamycins
(e.g. rifamycin), antimycotics (e.g. polyenes and benzofuran derivatives),
.beta.-lactams (e.g. penicillins and cephalosporins), chloramphenical
(including thiamphenol and azidamphenicol), linosamides (lincomycin,
clindamycin), macrolides (erythromycin, oleandomycin, spiramycin),
polymyxins, bacitracins, tyrothycin, capreomycin, vancomycin, tetracyclines
(including oxytetracycline, minocycline, doxycycline), phosphomycin and
fusidic acid.
Additionally, the polypeptides are well suited to formulation as sustained
release dosage forms and the like. The formulations can be so constituted
that they release the active polypeptide, for example, in a particular part
of the intestinal or respiratory tract, possibly over a period of time.
Coatings, envelopes, and protective matrices may be made, for example, from
polymeric substances, such as polylactide-glycolates, liposomes,
microemulsions, microparticles, nanoparticles, or waxes. These coatings,
envelopes, and protective matrices are useful to coat indwelling devices,
e.g., stents, catheters, peritoneal dialysis tubing, draining devices and
the like.
For topical administration, the therapeutic agents may be formulated as is
known in the art for direct application to a target area. Forms chiefly
conditioned for topical application take the form, for example, of creams,
milks, gels, dispersion or microemulsions, lotions thickened to a greater or
lesser extent, impregnated pads, ointments or sticks, aerosol formulations
(e.g., sprays or foams), soaps, detergents, lotions or cakes of soap. Other
conventional forms for this purpose include wound dressings, coated bandages
or other polymer coverings, ointments, creams, lotions, pastes, jellies,
sprays, and aerosols. Thus, the therapeutic polypeptides of the invention
can be delivered via patches or bandages for dermal administration.
Alternatively, the polypeptide can be formulated to be part of an adhesive
polymer, such as polyacrylate or acrylate/vinyl acetate copolymer. For
long-term applications it might be desirable to use microporous and/or
breathable backing laminates, so hydration or maceration of the skin can be
minimized. The backing layer can be any appropriate thickness that will
provide the desired protective and support functions. A suitable thickness
will generally be from about 10 to about 200 microns.
Ointments and creams may, for example, be formulated with an aqueous or oily
base with the addition of suitable thickening and/or gelling agents. Lotions
may be formulated with an aqueous or oily base and will in general also
contain one or more emulsifying agents, stabilizing agents, dispersing
agents, suspending agents, thickening agents, or coloring agents. The active
polypeptides can also be delivered via iontophoresis, e.g., as disclosed in
U.S. Pat. Nos. 4,140,122; 4,383,529; or 4,051,842. The percent by weight of
a therapeutic agent of the invention present in a topical formulation will
depend on various factors, but generally will be from 0.01% to 95% of the
total weight of the formulation, and typically 0.1-85% by weight.
Drops, such as eye drops or nose drops, may be formulated with one or more
of the therapeutic polypeptides in an aqueous or non-aqueous base also
comprising one or more dispersing agents, solubilizing agents or suspending
agents. Liquid sprays are conveniently delivered from pressurized packs.
Drops can be delivered via a simple eye dropper-capped bottle, or via a
plastic bottle adapted to deliver liquid contents dropwise, via a specially
shaped closure.
The therapeutic polypeptide may further be formulated for topical
administration in the mouth or throat. For example, the active ingredients
may be formulated as a lozenge further comprising a flavored base, usually
sucrose and acacia or tragacanth; pastilles comprising the composition in an
inert base such as gelatin and glycerin or sucrose and acacia; and
mouthwashes comprising the composition of the present invention in a
suitable liquid carrier.
The pharmaceutical formulations of the present invention may include, as
optional ingredients, pharmaceutically acceptable carriers, diluents,
solubilizing or emulsifying agents, and salts of the type that are available
in the art. Examples of such substances include normal saline solutions such
as physiologically buffered saline solutions and water. Specific
non-limiting examples of the carriers and/or diluents that are useful in the
pharmaceutical formulations of the present invention include water and
physiologically acceptable buffered saline solutions such as phosphate
buffered saline solutions pH 7.0-8.0.
The polypeptides of the invention can also be administered to the
respiratory tract. Thus, the present invention also provides aerosol
pharmaceutical formulations and dosage forms for use in the methods of the
invention. In general, such dosage forms comprise an amount of at least one
of the agents of the invention effective to treat or prevent the clinical
symptoms of a specific infection, indication or disease. Any statistically
significant attenuation of one or more symptoms of an infection, indication
or disease that has been treated pursuant to the method of the present
invention is considered to be a treatment of such infection, indication or
disease within the scope of the invention.
Alternatively, for administration by inhalation or insufflation, the
composition may take the form of a dry powder, for example, a powder mix of
the therapeutic agent and a suitable powder base such as lactose or starch.
The powder composition may be presented in unit dosage form in, for example,
capsules or cartridges, or, e.g., gelatin or blister packs from which the
powder may be administered with the aid of an inhalator, insufflator, or a
metered-dose inhaler (see, for example, the pressurized metered dose inhaler
(MDI) and the dry powder inhaler disclosed in Newinan, S. P. in Aerosols and
the Lung, Clarke, S. W. and Davia, D. eds., pp. 197-224, Butterworths,
London, England, 1984).
Therapeutic polypeptides of the present invention can also be administered
in an aqueous solution when administered in an aerosol or inhaled form.
Thus, other aerosol pharmaceutical formulations may comprise, for example, a
physiologically acceptable buffered saline solution containing between about
0.1 mg/ml and about 100 mg/ml of one or more of the polypeptides of the
present invention specific for the indication or disease to be treated. Dry
aerosol in the form of finely divided solid polypeptide that are not
dissolved or suspended in a liquid are also useful in the practice of the
present invention. Polypeptides of the present invention may be formulated
as dusting powders and comprise finely divided particles having an average
particle size of between about 1 and 5 .mu.m, alternatively between 2 and 3
.mu.m. Finely divided particles may be prepared by pulverization and screen
filtration using techniques well known in the art. The particles may be
administered by inhaling a predetermined quantity of the finely divided
material, which can be in the form of a powder. It will be appreciated that
the unit content of active ingredient or ingredients contained in an
individual aerosol dose of each dosage form need not in itself constitute an
effective amount for treating the particular infection, indication or
disease since the necessary effective amount can be reached by
administration of a plurality of dosage units. Moreover, the effective
amount may be achieved using less than the dose in the dosage form, either
individually, or in a series of administrations.
For administration to the upper (nasal) or lower respiratory tract by
inhalation, the therapeutic polypeptides of the invention are conveniently
delivered from a nebulizer or a pressurized pack or other convenient means
of delivering an aerosol spray. Pressurized packs may comprise a suitable
propellant such as dichlorodifluoromethane, trichlorofluoromethane,
dichlorotetrafluoroethane, carbon dioxide or other suitable gas. In the case
of a pressurized aerosol, the dosage unit may be determined by providing a
valve to deliver a metered amount. Nebulizers include, but are not limited
to, those described in U.S. Pat. Nos. 4,624,251; 3,703,173; 3,561,444; and
4,635,627. Aerosol delivery systems of the type disclosed herein are
available from numerous commercial sources including Fisons Corporation
(Bedford, Mass.), Schering Corp. (Kenilworth, N.J.) and American Pharmoseal
Co., (Valencia, Calif.). For intra-nasal administration, the therapeutic
agent may also be administered via nose drops, a liquid spray, such as via a
plastic bottle atomizer or metered-dose inhaler. Typical of atomizers are
the Mistometer (Wintrop) and the Medihaler (Riker).
Furthermore, the active ingredients may also be used in combination with
other therapeutic agents, for example, pain relievers, anti-inflammatory
agents, antihistamines, bronchodilators and the like, whether for the
conditions described or some other condition.
The present invention further pertains to a packaged pharmaceutical
composition for controlling microbial infections such as a kit or other
container. The kit or container holds a therapeutically effective amount of
a pharmaceutical composition for controlling cardiac damage and instructions
for using the pharmaceutical composition for reducing the effects of
myocardial infarction. The pharmaceutical composition includes at least one
polypeptide of the present invention, in a therapeutically effective amount
such that the effects of myocardial infarction are minimized.
Claim 1 of 32 Claims
1. A method of increasing survival of
blood vessels by reducing apoptosis of blood vessel cells during or after
vascular injury in a patient consisting of administering to the patient a
therapeutically effective amount of platelet derived growth factor,
angiopoietin-2, and vascular endothelial growth factor, and thereby
increasing survival of blood vessels by reducing apoptosis of blood vessel
cells in the patient during or after vascular injury.
If you want to learn more
about this patent, please go directly to the U.S.
Patent and Trademark Office Web site to access the full


text:
|The Message (MSG)
|New International Version (NIV)
|34 "When he raised him from the dead, he did it for good - no going back to that rot and decay for him. That's why Isaiah said, 'I'll give to all of you David's guaranteed blessings.'
|34 The fact that God raised him from the dead, never to decay, is stated in these words: " 'I will give you the holy and sure blessings promised to David.'
|Published by permission. Originally published by NavPress in English as THE MESSAGE: The Bible in Contemporary Language copyright 2002 by Eugene Peterson. All rights reserved. (The Message Bible Online)
|Scripture quoted by permission. Quotations designated (NIV) are from THE HOLY BIBLE: NEW INTERNATIONAL VERSION®. NIV®. Copyright © 1973, 1978, 1984 by Biblica. All rights reserved worldwide. (New International Version Bible Online)


text:
Play this game during Bauuer or TNGHT:
TRAP and Blow
northside groove...southside groove....eastside groove...westside groove
Those who believe in telekinetics, raise my hand
- Kurt Vonnegut
nobody knows for sure
Can we pick team names?
Friday: Outkast, The Replacements, Girl Talk, Chromeo, AFI, The Afghan Whigs, Bastille, Jagwar Ma, Grouplove, Caravan Palace
Saturday: Muse, QOTSA, Pharrell, Foster the People, Empire of the Sun, Kid Cudi, Sleigh Bells, Cage the Elephant, CHVRCHES, Capitol Cities, Temples, Bombay Bicycle Club, Holy Ghost!, Bear Hands
Sunday: Arcade Fire, Beck, Neutral Milk Hotel, Trombone Shorty, Frank Turner, Surfer Blood, J Roddy Walston
Even though I look it, I'm not a cop.
Coachella 10, 12.1, 13.1, 14.2
Lalapalooza 94
Is there any chance Larry Craig was part of the "tapping" group?
i was in on this last year. you all are fools!!! HAHAHA!!! watch your necks coachella 2013
No Shirt
No Shoes
No Dice
Learn it. Know it. Live it.
lool? what the hell? who the fuck would take the time to organize teams of people to do this. especially while the music is going off. there are much more important things to be doing than blowing on people. Such as dancing to the music I paid top dollar to see. I think that you've been tricked into believe that people actually organize teams to do this.
How's the training going, champs!
Coachella: 2004, 2005, 2006, 2007, 2008, 2009, 2010, 2011, 2012w1, 2012w2, 2013w1, 2014w1
someone did this to me during sxsw this year.
Anyone care to join me for a game of Tap & Blow in my tent this year?
It's called "please punch me in the junk"
i was wondering if this "Tap & Blow" game is also played at the STAGECOACH Festival? jjhhmm...
Coachella: 2004, 2005, 2006, 2007, 2008, 2009, 2010, 2011, 2012w1, 2012w2, 2013w1, 2014w1


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4th Annual Indie-pendence Day Festival 2014
Gramercy & Flatiron
Fri Jul 4
Photograph: courtesy The PIT
Time Out says
Posted: Wed Jun 18 2014
The People's Improv Theatre is hosting a festival featuring some of the city's finest independent teams, with hours of shows from improv teams both new and established. There's also live music and plenty of booze and BBQ thrown in.
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@carlaschuchmanactive 9 months, 2 weeks ago
HEY EVERYONE! I am sorry I can't write anymore. I did a blog post on my blog, if you don't mind, I'll send you there. it's what I would write here too. People just don't know. They just don't know…..http://carleysense.com/?p=1346 View
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"This city's going to see some mobilization like they never did before," said the Rev. Al Sharpton at a meeting Tuesday night. Flanked by members of the Bell family, Nicole Paultre Bell, Trent Benefield and Joseph Guzman, Sharpton announced the tentative plan for boycotts, demonstrations and acts of civil disobedience that will comprise the official response to the "not guilty" verdict in the Sean Bell case.
Sharpton held a closed door meeting in Manhattan with community members and city leaders, many of whom were from Queens. The purpose was to outline plans for the coming weeks, the promised response after Sharpton's pledge to the media to "close this city down."
The meeting, held at the Midtown headquarters of the 1199 SEIU health workers union, lasted from shortly before 6 p.m. until nearly 8 p.m., when representatives from across the city began to trickle into the lobby and talk to members of the press.
One of the first people out the door was Sean Bell's father, William Bell, who recently made headlines with his wife, Valerie, for speaking out strongly against Detective Michael Oliver, whose 31 shots fired in the incident contributed to the death of their son.
"I'm here to get justice for my son," William Bell said. When asked whether he thought the demonstrations in the city might lead to violence, he was quick to dispel the notion "Peace, peace, peace. We got to have peace."
Bishop Lester Williams, the reverend who was to marry Sean and Nicole Paultre Bell the day Bell was killed, said he "thought the meeting was very productive," and while he didn't have an immediate timetable for how the upcoming events would play out, he characterized them as an "immediate response."
Several members of the City Council were in attendance, including John Liu, Hiram Monserrate, Matthieu Eugene, Charles Barron, Leroy Comrie, and James Sanders Jr.
"Every approach was discussed," Sanders said. "What the outcome will be, will be determined by the people in the streets." Sanders was also adamant that while the verdict had already been rendered in the case, there was still more to be said.
"There are many courts. One court is on Queens Boulevard, one court is on the streets, and the jury is still out for that court."
Sanders described the mood in the meeting as "somber, fiery and very determined."
Sharpton himself said that the meeting provided an opportunity to organize concerned citizens into several groups, some in charge of boycotts and civil disobedience, others in charge of organizing what he referred to as "a massive march."
Still another group, likely to include the City Council members in attendance and members of the state and federal legislatures, was banding together to tailor new legislation designed to protect civilians from tragic incidents like the one that befell Bell and his compatriots in late 2006.
Congressman Gregory Meeks, who has been among a handful of strong public advocates for the Bell family, is one of the legislators likely to try and push through new federal laws regarding police interaction with the public.
In an interview on his way to Washington, D.C., Meeks said he was pleased with the way the demonstrations were being organized thus far.
"People are galvanizing together and organizing together, an organized mass movement of folks, coming together all speaking for one thing, and that is that we're trying to get justice in this case," Meeks said. He also praised the Bell family, marvelling at what he called their patience and strength.
Sharpton had apparently issued a gag order at the meeting, because no one present was willing to talk about the exact timetable for events, or any concrete details about the locations or nature of the upcoming demonstrations.
One source who sat in on the meeting said many members of the community had advocated starting demonstrations as early as that night, but that a more likely start date was the end of this week.
Sharpton himself said the events would "roll out over the next 10 days."
He also admitted that all the demonstrations were targeting the U.S. justice department, and other legislative bodies which had the power to take action to affect a federal investigation into the case, and rewrite the legal code.
"We are a collective," Sharpton said. "This is not about one person."
Sharpton said he was willing to endorse non-sanctioned boycotts and civil disobedience as long as they were not destructive.


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Locations and Hours: Morristown (973) 538-7773 Randolph (973) 584-7773 Hackettstown (908) 852-1650
Top 100 Bicycle Retailer in the United States
Marty's has been voted one of the top 100 Bicycle Retailers in the United States for the last 7 years in a row by Bicycle Retailer and Industry News. Thanks to our loyal customers and employees!
Here is our blurb from the industry publication:
Best Bike Shop in New Jersey
New Jersey Monthly Magazine readers have voted Marty's Reliable Cycle the best bike shop in New Jersey for 2012. Thanks to our loyal customer and employees!
Here is our blurb from the magazine: (or view it on the NJ Monthly website)
The three locations of Marty's Reliable Cycle in Morristown, Randolph and Hackettstown remain committed to "not just selling a product, but selling a lifestyle," says owner Marty Epstein. That lifestyle includes cycling events—like the Gran Fondo. On September 9, Marty's will hold its second Gran Fondo, with four rides of varying lengths benefitting local charities. Last year's event drew 1,000 registrants; this year, Epstein is expecting 2,500 riders. (martysreliable.com) RUNNERS-UP:Brielle Cyclery, BrielleThe Peddler, Long BranchBeachwood Bikes, Beachwood
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First it's Adele, now it's a whole country of people. When will your reign of ocular judgement and subsequent verbal terror end, Karl?!
Lagerfeld went for round...whatever it is...with WWD, and decided to share his thoughts towards the entire population of Japan, since he's back in the country for the first time in about eight years, promoting his new book of photography. Japan has changed, says Karl. Oh yes, it has.
"It's changed a lot but it's changed for the better I think. I noticed that people became bigger than before because now they eat more cake and sweets and things like this that they didn't do in the past. There's a real change in the look of the Japanese people. Normally, before, they were all tiny. It's the kind of beauty you get from junk food."
Okay, so I think this is Karl trying to weirdly compliment Japan. But you know, the man doesn't know how to just say "Japan is great, I like it here even better than before", like a normal person. He has to say, in a roundabout way, that everyone in Japan eats junk and has gained weight. And then, of course, he says it's a good thing because he doesn't want another Adele-gate. We all know how you really feel Karl. We can read you like a book.
And it's kind of likely that Lagerfeld isn't exactly up-to-date on Japan's day-to-day diet, since he hasn't been there for eight years. "Cake and sweets" aren't necessarily the culprit here - I know someone from Japan who blames the increase in size (and they say there is one) on a more westernized diet with more meats and not necessarily more junk food. Facts are important sometimes, man.
Perhaps, maybe, just possibly, he should just give a generic response for once, something that doesn't make him sound like a haughty, weight-obsessed fashion maven that doesn't exactly have the tightest grip on what real life is. Just a suggestion, Karl. No offense. (via HuffingtonPost)
Do you think celebrities should put more thought into what they say and how they present themselves to publications?


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Alright, I figured it out. Lets just say Im not too clever. I love the layout, thankyou me. Second layout that Ive done myself and love. I love the icon but will hopefully find a better one. Thats all for now.
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|12th Annual Confederate Memorial Service
Under the Bamberg County Confederate Memorial, the 12th annual Confederate Memorial Service honored the service of Confederate veterans on the grounds of the Bamberg County courthouse, to the sacrifices and heroism of Confederate soldiers.
With music played by Evelyn and L.A. Gardner of the Sleytown Players, Pete Boineau, Commander of Rivers Bridge Camp 842 of the Sons of Confederate Veterans gave opening remarks, Nancy Foster read from passages of the History of Bamberg County, South Carolina, and celebrated local historian and story-teller Betty Jane Miller spoke eloquently of the need to keep the record straight amidst the rewriting of the true history of the South and the war between the states conflict.
The Confederate Memorial, she explained, tells the story of a collection of gallant men who fought for states rights and who died to preserve those rights.
In April 1910, the women organized the Francis Marion Bamberg Chapter, U.D.C (United Daughters of the Confederacy). They named it in honor of Francis Marion Bamberg, who was called "general" because of his position as brigadier general on the staff of Governor Wade Hampton.
Bamberg enlisted as a corporal in Company A, the Hampton Legion Artillery Battalion. He remained with this company an was promoted to lieutenant when the company was detached from the Hampton Legion and re-designated, first, as the Washington Artillery, and later, as Hart's Company Horse Artillery. (Source: A Guide to Confederate Monuments in South Carolina: "Passing the Silent Cup" by Robert S. Seigler, 1997, pg. 62.)
Under the guidance of chapter president Mrs. Frank G. Bamberg, the members untiringly took up the work of acquiring the funds -- $3,000 donated by 400 subscribers. The marble figure of a Confederate private at parade rest was carved in Italy. It stands on an eighteen-foot shaft of South Carolina granite, which rests on an eleven-foot pedestal. The women of the U.D.C. left the original eastern side, now the northeastern side, blank. They intended to place a bronze tablet on the east side engraved with the names of the Confederate soldiers who were from the part of South Carolina that became Bamberg County in 1897. This goal was never met.
The cornerstone was laid on Confederate Memorial Day, May 10, 1911...Bamberg's businesses and schools were closed for the exercises. Six hundred people, including two hundred school children, attended. Rev. W. H. Rodgers, pastor of the Bamberg Methodist Church, gave the opening prayer. The master of ceremonies was Dr. James Benjamin Black, a physician and state senator who had begun the process that resulted in the formation of Bamberg County...The thirty-five foot monument was unveiled on October 26, 1911. The monument was moved to its present location in 1950.
Ed Moody, past Commander of Rivers Bridge Camp 842 gave the roll call of the Bamberg Confederate Soldiers, and Capt. Eddie Williams of Hutto Chapel Baptist Church read off the roll call of African American Soldiers as the bell rang between each name.


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|Property type
|Minimum Stay
|5 - 7 nights
Welcome to our secluded oceanfront dream retreat. 'Sea Nest' is a newly furnished 1 bedroom, 1 bathroom attached studio/loft suite that can sleep 2 people and is ideal for adult couples. This property is the perfect 'location' for a private oceanfront getaway! Your retreat is located about twenty five feet from the crystal blue ocean that gently laps up to your private rock and sand beach. Interior features include a small kitchenette, ceiling fans, air conditioning, flat screen TV with cable, wireless internet, ipod docking system, and cd/dvd player.
Exterior features include Weber gas grill, table and chairs for outside dining, your own private beachfront with chairs, kayaks, and snorkel gear to enjoy the tropical fish and coral reefs in the cool, sparkling Caribbean waters at your doorstep. The property has an abundance of beautiful tropical plants that surround you including your own 'paradise trail' to the sea. Listen to the tree frogs at night and watch the hummingbirds, bananaquits, and iguanas during the day. One of my favorite things is to lie in bed and hear the relaxing sound of the surf gently lapping the shoreline. You are a 10 minute walk to the Westin resort and a 5 minute drive to Cruz Bay. We strive to keep our property crystal clean and maintained for your safety and enjoyment.
Keywords: Loft, Studio ideal for adventurous couples!! Enjoy two FREE KAYAKS! FREE SNORKEL GEAR, BEACH CHAIRS & COOLERS!. Tropical reef with Lobster! Explore the rocks along the seashore. BBQ! Just bring your swimwear & sunscreen!! Steps to your own beach!!
We are life loving and love hanging out in nature on St. John.
We enjoying sailing and embracing new adventures! St. John
is in our hearts- whenever we leave she always draws us back!
Come enjoy paradise with us.
Paul & Joan purchased this studio in 2008
We chose Chocolate Hole for many reasons. We wanted to be located directly on the ocean with our boat in front of the property. This spot we found is truly amazing! Our home is twenty five feet from a reef just teaming with gorgeous tropical fish and sea turtles. The location is just minutes to groceries, shopping and incredible dining. we love it here!! We know you will too!! Whiners and complainers stay away, please.
This property is not for those that come to sit and watch videos or peck on their laptops all day. This property is for folks that want to explore the true island wildlife- not Woodys! Just kidding....
Hi Paul and Joan,
Just wanted to send a quick note to say how much I (and my sister) really loved staying at Sea Nest. It was the perfect getaway - the accomodations were just right, we kept commenting on how nicely decorated it was with the island theme. The location was perfect, close enough to Cruz Bay to enjoy the ammenities but far enough from the hustle and bustle (if you can call it that!) to feel like we had our own private abode in the islands! If I were to give a suggestion it would be to add more towel bars or a drying rack. The snorkel gear, beach chairs and coolers provided everything we needed for beach excursions and my snorkeling in Chocolate Hole was one of the most EXCITING with the barracuda and sea turtle sightings. It was a perfect vacation, will definitely be back!
Thank again!
We offer two kayaks and snorkel gear! There are some amazing
hiking trails on St. John- you can get great info and maps at National Park visitor center. We provide information on day sails and trips see the BVI's- highly recommended. Plenty of fun things to explore and discover! You will not be bored here! See you soon.....
|Rate Period
|Weekend Night
Dec 20 - Apr 30
Dec 20 2014 - Apr 30 2015
5 night minimum stay
|Tax Rate
Payment is usually accepted in the quoted currency (USD) unless the currency and the amount is specifically agreed in advance with the owner / advertiser.


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- Free Trials
- Download Fact Sheet
- Download Lesson Overview
- Federal Funds Available for Pathways: Science
- Download White Paper: Targeting Science Misconceptions in Middle School Students
- Subscribers: Visit our Professional Development page to learn about free webinar training, private webinars, and face-to-face workshops.
Pathways: Science
Transform Misconceptions into Understanding
through Inquiry-Based Exploration
How does an animal grow larger—cell growth? cell reproduction?
Each of its cells divides repeatedly, producing two new cells each time.
What is inside bubbles when water boils—air? water molecules? nothing?
Water molecules. Boiling maintains the identity of a water molecule.
Winner of the 2014 Teachers' Choice Award, Pathways: Science is an online, interactive approach to teaching the scientific method in grades 6, 7, and 8. Its framework is ideal for project-based learning, teacher-led instruction, and STEM programs.
Focus on Misconceptions Systematically
With 100 lessons tied to the curriculum, Pathways: Science uses a consistent Predict-Investigate-Conclude process that promotes inquiry-based learning, critical thinking, and conceptual change.
Support Next Generation Science, Common Core ELA, and State Standards
Students learn to reach conclusions by comparing and contrasting information, determining central ideas, evaluating arguments, and analyzing evidence.
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Extensive lesson guidance—flexible lesson plans, searchable standards correlations, and worksheets—saves preparation time for teachers.
Awards And Accolades
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—Tech & Learning, January 2014
"Highly Recommended "
—Library Media Connection, September 2012
"…an excellent curricular support service for the middle school…Recommended."
—Internet@Schools, June 2012
Common Core Standards
- Read and comprehend informational texts.
- Integrate and evaluate content presented in diverse forms of media.
- Integrate quantitative or technical information expressed in words in a text with a version of that information expressed visually (e.g. in a flowchart, diagram, model, graph, or table).
- Compare and contrast the information gained from experiments, simulations, video, or multimedia sources with that gained from reading a text on the same topic.


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RELEASED: Sept. 1, 2011
Mark your calendar
EAU CLAIRE — Librarians at the University of Wisconsin-Eau Claire McIntyre Library have committed to providing greater and more immediate access to scholarly research. By signing an Open Access Declaration, the library joins other academic libraries around the world in making more resources available to students and researchers.
According to John Pollitz, McIntyre Library director, open access removes barriers to information.
"Libraries across the country have seen their budgets squeezed by unsustainable inflation of journal prices. Resulting journal cancellations have hampered our ability to provide access to information that is the lifeblood of higher education," Pollitz said. "As librarians, we support the open access movement as a way to reverse this trend and expand access to scholarship."
Open access has the power to transform the way research and scientific inquiry are conducted and has direct and widespread implications for academia, medicine, science, industry and society as a whole, according to the Scholarly Publishing and Academic Resources Coalition. It expands access to scholarly information from all disciplines by making research available through such online repositories as arXiv and PubMed Central, as well as institutional repositories like Minds@UW, a digital collection of UW System research and scholarship. Through the Open Access Declaration, McIntyre Library faculty have committed to depositing their scholarship in Minds@UW or other appropriate repositories.
Many publishers allow authors to submit a preprint to an institutional or subject repository. Authors can often negotiate a publishing agreement, also known as a copyright transfer agreement, to make a version of their publication freely available in institutional repositories like Minds@UW or on their faculty webpage.
To build awareness at UW-Eau Claire, McIntyre Library will host a series of presentations and discussions during Open Access Week, Oct 24-28, regarding the implications of open access for scholarship and higher education. Faculty and students can learn more about their rights as authors and learn about the tools for open access publishing and research.
For more information about open access at UW-Eau Claire, contact John Pollitz, McIntyre Library director, at 715-836-4827 or email@example.com or visit the McIntyre Library website for a complete schedule of Open Access Week activities.
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Channel 6 News - Search Results
Union's Final Practice Before Frozen Four
Schenectady, NY - After receiving two commemorative sterling silver, garnet encrusted hockey pucks from Northeastern Fine Jewelry at Monday's official send-off party, the Union hockey team got back onto the ice for its final home practice of the season.
The No. 1 ranked Dutchmen head to Philadelphia Tuesday at 1:00pm. They'll face Boston College in Thursday's semifinal round of the Frozen Four.


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We fear things in proportion to our ignorance of them.Livy
We cannot be saved until we have risen above all our enemies, not the least of which is ignorance.Joseph Smith
True friendship can afford true knowledge. It does not depend on darkness and ignorance.Henry David Thoreau
To become educated is to move from cocksure ignorance to thoughtful uncertainty.Unknown
One part of knowledge consists in being ignorant of such things as are not worthy to be known.Crates
Nothing in education is so astonishing as the amount of ignorance it accumulates in the form of facts.Henry Brooks Adams
Nothing in the world is more dangerous than a sincere ignorance and conscientious stupidity.Martin Luther King Jr
Nothing is more terrible than ignorance in action.Johann Wolfgang von Goethe
Ignorance is never out of style. It was in fashion yesterday, it is the rage today and it will set the pace tomorrow.Frank Dane
The essence of knowledge is, having it, to apply it; not having it, to confess your ignorance.Confucius
The truest characters of ignorance Are vanity, and pride, and annoyance.Samuel Butler
Ignorance is preferable to error, and he is less remote from the truth who believes nothing than he who believes what is wrong.Thomas Jefferson
Ignorance is not so damnable as humbug, but when it prescribes pills it may happen to do more harmGeorge Eliot
Ignorance, when it is voluntary, is criminal; and he may be properly charged with evil who refused to learn how he might prevent itSamuel Johnson
There is no means by which men so powerfully elude their ignorance, disguise it from themselves and from others as by wordsGamaliel Bradford
The whole family of pride and ignorance are incestuous, and mutually beget each otherCharles Caleb Colton
His ignorance covers the world like a blanket, and there's scarcely a hole in it anywhereMark Twain
Ignorance is not privileged by titular degreesLatin Proverb
Ignorance gives one a large range of probabilitiesGeorge Eliot
I do not approve of anything which tampers with natural ignorance.Oscar Wilde
Mystery is another name for our ignorance; if we were omniscient, all would be perfectly plainTryon Edwards


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Community category
A new paradigm for transportation using a network of unmanned aerial vehicles.
Detailed Description:
Matternet Inc. is a startup based in Palo Alto, California, founded by Andreas Raptopoulos, Paola Santana, Dimitar Pachov and Darlene Damm. Matternet Inc. was formed after developing the fundamental business concepts as part of a team project at Singularity University during the summer of 2011. Meet the Singularity University project team here. Industrial and Vehicle design by Ido Baruchin.
Known drawbacks of design:
Designed in:
Status of realization:
Health, Mobility
Region of use:
Africa, Asia, Europe, North America, Oceania, South America
With Matternet, a rural villager can order medicine required using their mobile phone. Next, the medicine is loaded onto a UAV, also known as a "grasshopper". The grasshopper is sent to the villager and navigates the precise drop-off point – aided by a beacon transmitted from a landing pad at the destination. This ambitious idea will be rolled out in three phases: I: Capable of transporting 1-2 kilograms of cargo will be "aircraft kits" including plug-in charges and a quadracopter drone, or grasshopper. II: Solar-powered stations recharge autonomous aircraft capable of transporting 50 – 100 kilograms of cargo. III: Networks of grasshoppers expand and overlap. This AI driven infrastructure will integrate city and village and be able to transport 500 – 1000 kilograms of cargo.
Matternet, designed by an international team of business, design and engineering experts, is an ingenious solution to the problem of unequal access. Spawned from The Singularity University, it aims to create a roadless transportation network. Justine Lam, the Matternet project manager, explains, "we want to use a network of unmanned aerial vehicles (UAVs) connected by robotic ground stations and an AI driven software system. We want to do what the Internet did for information but do that for physical things".
In Africa, there are fewer roads in the continent today than 30 years ago because of poor maintenance. Similarly, in Myanmar only 11.8% of the roads are paved and in Cambodia, only 20% of the roads are paved and in passable condition. Due to a lack of roads, ports, bridges and trains, it is estimated that one billion people have inadequate access to food, water, medicine, and other supplies. This exclusion extends to the exchange economies, in which those from geographically isolated communities are unable to connect to. Without access to social and economic systems, potential paths out of poverty remain blocked.
Is the design protected by patent or ip registration?
How has the development of the design been financed hereunto?
Company development costs
Is there a plan for future investments?
Is there in-house competencies to secure market roll out of the design, with regards to investment, distribution, sales, etc.?
Designed by:
Andreas Raptopoulos and Paola Santana.
Professional status of designer:
United States of America
City/Country of residence:
United States of America
Designed by:
Dimitar Pachov and Darlene Damm
Professional status of designer:
United States of America
City/Country of residence:
United States of America


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Business schools love teamwork. Here's what one student thinks:
What's that thing economists are always worried about? Ah yes … unintended consequences.
Via I Love Charts.
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Boy I couldn't agree more. I ran into many of the same problems during my CS degree.
I wonder if we couldn't improve the performance of these groups by permitting a subset of the class to pick their group-mates, then have them run through a number of smaller problems.
Each time, the group leaders are permitted to re-pick their group. Any students left over at the end are forced into their own group. That would provide a much stronger incentive for students to avoid free-riding on the efforts of their classmates.
I really like this suggestion.
But, there are two problems. First, students don't like being judged publicly, and they tend to blame the professor on their evaluations when this happens. It's shocking how prickly they are. Second, administrators rely on student evaluations far more than they should, so the first point would end up being a game killer.
It is a good thing schools online teach business degree courses too!
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on orders over $75
Zoo Med All Natural New Zealand Sphagnum Moss
|Zoo Med's All Natural New Zealand Sphagnum Moss is a very lush carpet like moss. New Zealand moss is preferred over any type of for terrarium use due to its softness and ability to hold moisture longer. This specific moss can hold moisture for up to 20 times its dry weight! Great for live plants & long lasting Holds more water & stays moist longer Natural compounds prevent decomposing in humid environments Excellent top substrate For use with most frogs, toads, salamanders, newts and invertebrates including hermit crabs. Can also be used with small snakes.


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Call our helpful, friendly team of advisors on : 01572 332 032Online customer service lines open Mon-Fri, 9.30am-5pm (UK time)Shops open Mon - Sun 09.00 - 17.30
At Rutland Cycling, we're here to help. We know you just want to get out riding, so we've put together this Help section, to give you instant answers to your questions. View our Help Section
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Top Lodge,
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Term Time:
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Sat: 09:00-17:30
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Every day: 09:00-17:30
Opening Times:
Mon: 09:00-18:00
Tues: 09:00-18:00
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Elegantly nestled amidst a historic mixed broadleaf and conifer woodland, our Fineshade bike shop is the newest of our stores and is entering its third year.
We are a buzzing Forestry Commission Trail Centre with something for both the family and the more experienced rider. In store we have the best brands for bikes, clothing, parts and accessories. Outside, you can explore acres of beautiful ancient woodlands with the opportunity of seeing some incredible wildlife including one of many red kites, in their adopted habitat.
We have a thriving cycle hire offering at our Fineshade store that works in tandem (no pun intended) with the new trails that we are constantly developing with the Forestry Commission.
Just outside the store is a quaint cafe serving an excellent selection of cake, coffees and sandwiches; perfect to recharge after a day in the saddle.
We have a number of different cycling routes available including:-
Beginner: a family cycle route that features 8km of green woodland trail and is suitable for all abilities.
Intermediate: A series of skills loops suited perfectly to keen youngsters and newcomers to the MTB scene.
Intermediate-Advanced: Renowned Wakerley Blue Route - 5km of singletrack thrills. Please call ahead to check track conditions.
Also in store, we have a fantastic workshop that is staffed by Cytech accredited mechanics and an active rides and events calendar.
It's fair to say that if you come down to the woods today you're in for a super ride!
Rutland Outdoor Shop at Fineshade Wood
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