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Westonbirt, Gloucestershire
Westonbirt, now known as the National Arboretum, has a spectacular display of autumn colour. It boasts Britain's largest collection of Japanese maples, which flame in vivid berry colours with splashes of saffron and orange. A specially designed seasonal trail snakes between towering oaks, beeches and horse chestnuts. There are play areas and quizzes for children to answer as they walk around.
More info 01666 880220; forestry.gov.uk/westonbirt.. Open daily, adults £7.50, children £2.
Stay at the Priory Inn (01666 502251; prioryinn.co.uk) in Tetbury, which combines fantastic gastro-pub food (excellent quirky English tapas menu) with sleek rooms in calm neutral colour schemes. From £109. [All prices are for a double room for two, with breakfast, unless stated.]
Stourhead Gardens, Wiltshire
One of the most beautiful National Trust properties, with landscaped gardens tumbling down to a vast lake. The grounds are dotted with classical temples and follies and in the autumn tulip trees glow buttery-gold and American maples light up with scarlet hues. There are five waymarked walks across the estate. You should allow a whole day to do this utterly beautiful garden justice. A fantastic on-site restaurant uses produce from the estate's kitchen gardens.
More info 01747 841152; nationaltrust.org.uk. Open daily, garden £6.60 adults, £3.60 children.
Stay at Bishopstrow House (01985 212312; bishopstrow.co.uk) in Warminster, a classic country house hotel with opulent rooms, rolling grounds and an elegant spa with a large indoor pool. From £149.
The High Weald, Kent
Make a weekend of it by visiting a clutch of properties located close together. Bedgebury Pinetum is fantastic for families, with tree walks, playgrounds, boating and acres of parkland draped in scarlets and yellows. Garden lovers should visit Marle Place, a privately owned garden that glows scarlet and gold in the autumn, and Scotney Castle, a romantic garden built around a 14th-century ruin. Bewl Water, a reservoir surrounded by lush countryside, is also close by.
More info 01892 515675; sevenwonders.org.uk. Prices vary.
Stay at the George Hotel in Cranbrook (01580 713348; thegeorgehotelkent.co.uk), which blends contemporary style with medieval architecture. From £80.
Alice Holt Forest, Surrey
An ancient stretch of woodland famous for its oak trees - which once supplied timber for naval ships - and more recently as a location for the film Gladiator. There are waymarked trails and cycle hire facilities at weekends and in school holidays, with play areas and picnic spots throughout.
More info 01420 23666; forestry.gov.uk. Open all year. Free.
Stay at the Bishop's Table (01252 710222; bishopstable.com) in the heart of Farnham, which is renowned for its food. From £75.
Carbisdale, Inverness, Scotland
Woods cascade down to a stunning loch and are dominated by Carbisdale Castle, built in 1917 as a home for the Duke of Sutherland's widow and now a youth hostel. Mature oak trees mix with Scots pine. There are two waymarked walks with glorious views across the Dornoch Firth, as well as marked cycle trails. Walk to the Falls of Shin visitor centre, where you may spot salmon jumping in the river Oykel.
More info Open daily, access through Carbisdale Castle. Free.
Stay at Carbisdale Castle Youth Hostel (0870 155 3255; carbisdale.org), which has rooms sleeping from two to 14 and a restaurant. It is one of the most opulent youth hostels in the world. Beds from £15.50.
Arley Arboretum, Bewdley, Worcestershire
Arley has a spectacular collection of Japanese acers (maples) that glow like rhubarb and custard in the autumn, alongside grand oaks and towering beeches in flaming auburns and golds. Beneath the trees scurry the wildlife - badgers, stoats, squirrels, foxes and roe deer - that is almost as much of an attraction as the trees. Make it a family day out by travelling to Arley on the steam-driven Severn Valley Railway.
More info 01299 861368; arley-arboretum.org.uk. Open Weds-Sun, 11am-5pm, adults £4, children £1.
Stay at the Hundred House Hotel (01952 730353; hundredhouse.co.uk) in nearby Norton. Rooms are eccentrically chintzy but fun. The food is hearty gastropub fare. From £99.
Wendover Woods, Bucks
Perched on the edge of the Chilterns, Wendover Woods offers spectacular views across Aylesbury Vale, and in the autumn the huge, ancient beech trees along the Boddington Bank trail blaze in spectacular colours. The woods teem with badgers, foxes, weasels and deer, and twitchers head to Wendover to see the elusive firecrests and red kites. There is a good children's play area and information centre.
More info 01296 625825; forestry.gov.uk. Open daily, from 8am to dusk. Free.
Stay at Hartwell House (01296 747444; hartwell-house.com), a traditional country house hotel that is slick rather than stuffy. The grounds are stunning and there's a top-notch spa. Standard rates £290, but special offers from £175.
Whinlatter Forest, Cumbria
Billed as 'England's only mountain forest', Whinlatter comes alive in the autumn when the larches and broad-leaf woodland slowly turn from green to russet and bright lemon-yellow. There is an informative visitors' centre, showing the 14 miles of roads available to walkers and bikers, as well as waymarked footpaths. There is a forest playground and stunning views across to Grisedale Pike.
More info 01768 778469; visitcumbria.com/kes/whinfor.htm. Free.
Stay at the Pheasant Inn (01768 776234; the-pheasant.co.uk) in Cockermouth, a 500-year-old converted farmhouse with log fires, slap-up breakfasts and an impressive restaurant. From £75.
Lanhydrock, Cornwall
One of Cornwall's most glorious gardens, Lanhydrock reaches its spectacular best in the autumn, when scarlet acers and yellow tulip trees light up the parkland running down to the river Fowey.
There are numerous footpaths throughout the 900 acres of woodland, and the house itself - one of Britain's most complete 19th-century houses - is also worth exploring.
More info 01208 265950; nationaltrust.org.uk. Open daily, admission £5.30 adults, £2.65 children.
Stay at Hartswell Farm (01208 873419; connexions.co.uk/hartswell), a working 52-acre farm with four comfy rooms in a traditional 17th-century farmhouse. Breakfasts are seriously big. From £40.
Kielder Water And Forest, Northumberland
The largest man-made lake and forest in Europe, Kielder explodes in colours in the autumn, when stands of aspen, ash and stately oak trees glow strawberry-blond and auburn. Officially the country's most tranquil spot (according to the Campaign for Rural England), you can walk, bike, sail, ride or simply pick a spot to sit back and keep an eye out for the rare red squirrels.
More info 01434 220616; kielder.org. Open daily. Free.
Stay at the Pheasant Inn (01434 240382; thepheasantinn.com) near the reservoir, a comfortable pub with rooms, an excellent restaurant and cosy traditional bar. From £75.
Hyde Park, London
If you're after autumn colours in an urban landscape, they don't come much better than Hyde Park, which has more than 4,000 trees in 350 acres. Stroll along Rotten Row between beeches and russet and gold horse chestnuts, or up to Kensington Palace through a carpet of buttery yellow leaves. The Lido cafe is the perfect spot for a pause and warming hot chocolate.
More info 020 7298 2000; royalparks.org.uk. Open daily, 5am-midnight. Free.
Stay at The Dorchester (0207 629 8888; thedorchesterhotel.com), directly opposite the park. Gloriously over the top and utterly indulgent, it's pricey but worth it. From £205.
Bodnant Garden, Conwy, Wales
Bodnant has a spectacular location, on the river Conwy with stunning views across to Snowdonia. The 80 acres include a terraced garden, a 'wild' garden and informal lawns shaded by trees that glow purple, scarlet and gold. The botanical collections are particularly impressive, with plants from China, North America and Europe.
More info 01492 650460; bodnantgarden.co.uk. Open daily until 4 November. Adults £7, children £3.50.
Stay at Sychnant Pass House (01492 596868; sychnant-pass-house.co.uk), a charmingly informal country house, with beautiful gardens and memorable suppers. From £95
Aberglasney, Wales
Many of the trees and shrubs have been specifically planted for their autumn colours. Stroll beneath the deciduous trees in Pigeon House Wood, under the yew tunnel or around the beautifully manicured cloister gardens. This is a delightfully intimate garden, with a unique 'ninfarium' - a garden created in the ruined central rooms and courtyard of the adjoining mansion. There is even a restored parapet walk above the cloisters, which gives stunning views.
More info 01558 668998; aberglasney.org. Open daily, adults £6.50, children £3.00
Stay at Glascoed Farm (01994 231260; glascoedfarm.co.uk), a working dairy farm, with one double room and a cottage sleeping four. Breakfasts are memorable. From £50.
Rannoch Forest, Scotland
Draped along the shores of Loch Rannoch, the forest is in autumn a buttery-rust mix of oak, aspen, birch and willow. Berry-laden shrubs such as rowan, rose, crab apple and hawthorn punctuate the undergrowth with splashes of scarlet and purple. There are waymarked walks, and regular appearances by red squirrels, pine martens and curlews.
More info 01350 727284; perthshirebigtreecountry.co.uk. Free.
Stay at Macdonald Loch Rannoch resort (0870 194 2112; loch-rannoch.com), which is surrounded by beautiful woodland and offers off-roading and quad-biking through the forest. From £40.
The New Forest, Hampshire
The New Forest offers miles of deciduous woodland, with dramatic canopies of oak and beech. There are cycle tracks and waymarked walking trails.
More info 01590 689000; thenewforest.co.uk. Free.
Stay at New Forest Living (0845 680 0173; newforestliving.co.uk), which has cottages of all sizes.
Anglesey Abbey, Cambridgeshire
This elegant Jacobean country house is set in 98 acres of landscaped gardens, with individual walks and lawns dominated by towering trees, including red oaks, sycamore and limes. Yellow field maples dominate the Temple Lawn, while the Pilgrim's Lawn has been planted with shrubs and trees to give a gorgeous autumn spread. Autumn crocuses form a carpet of pastel mauves beneath the falling leaves.
More info 01223 810080; nationaltrust.org.uk. The house and gardens are open Wednesday-Sunday, 10.30am-5.30pm until 28 October. Gardens are open until 23 December, 10.30am-4.30pm. House and gardens £8 adult, £4 child. Garden only £4.40/£2.20.
Stay at the new Hotel du Vin (01223 227330; hotelduvin.com) in Cambridge. Predictably slick, with an atmospheric bar tucked away in labyrinthine cellars. From £135.
Sheffield Park Garden, East Sussex
Five linked lakes create dramatic reflections of the vivid autumn colours that flood Sheffield Park from Japanese maples, swamp cypresses, birches and tupelo trees in flaming ochre and scarlet. Designed by Capability Brown, the 18th-century garden mixes manicured lawns with stands of beech and oak trees and beds of autumn gentians. There are designated walks, children's trails and quizzes.
More info 01825 790231; nationaltrust.org.uk. Open daily until 4 November, Tuesday to Sunday thereafter. £6 adults, £3.10 children.
Stay at Ockenden Manor (01444 416111; hshotels.co.uk), a picturebook Elizabethan manor house with nine acres of gardens and cosy, firelit lounges. From £170.
Kew Gardens, London
Autumn colours are at their most dramatic in the Woodland Garden, where maples add splashes of cherry-red and butter-yellow to the cyclamens, belladonna lilies and crocuses that poke their heads through the carpet of leaves. Kids will love the interactive botanical displays, quizzes and trails.
More info 0208 332 5655; kew.org. Open daily, adults £12.50, children free.
Stay at Hotel 55 (0208 991 4550; hotel55-london.com) which is bizarrely located on the busy North Circular Road, but is sleek and elegant and has a cosy lounge bar. From £85.
Sherwood Forest, Nottinghamshire
The pine trees that dominate Sherwood Forest make a stunning backdrop for the reds and oranges of the birch, oak, sweet chestnut and beech. The forest covers 20 miles, with plenty of waymarked walking trails and cycle paths. Haywood Oaks is one of the most dramatic parts of the forest, where some of the oak trees are several hundred years old.
More info 0845 3673787; forestry.gov.uk. Free.
Stay at Center Parcs (08700 673030; centerparcs.co.uk), in the heart of the forest. A two-bedroom villa costs from £325 for a weekend break.
Winkworth Arboretum, Surrey
Created by horticulturist William Fox, this arboretum is filled with trees that give the best autumn colours - maples, mountain ash and whitebeam - amid more than 1,000 species of plant and shrub. There is a special walks leaflet listing 200 trees to identify, and a trail for children.
More info 01483 208477; nationaltrust.org.uk. Open daily, adults £5, kids £2.50.
Stay at Inn on the Lake (01483 419997; theinnonthelake.co.uk), a recently renovated pub with comfortable rooms and good wholesome food. From £69.


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Dirty and Offensive Christmas Songs!
The only way I can deal with the annual onslaught of cheery and/or solemn Christmas songs is to make up filthy, raucous versions of them and make those the official hymns of the season.
It's painfully immature, for sure, but it helps cut through the cheap sentiment and relentless faux glee that threaten to pollute our lives for a month or so while we stuff our feelings by stuffing our stockings.
How about:
"I'm dreaming of a tight Christmas/Just like the snatch I used to know"
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"I saw daddy felching Santa Claus..."
"All I want for Christmas are my two front tits..."
"In the meadow, we can blow a snowman..."
Help me out here, folks. Help me spread some more smutty cheer!
(PS: This post is dedicated to the salty duo the Duelling Bankheads, who just performed at Van Dam with their holiday classics "Frosty the Coke Whore" and "Here Comes Menopause.")
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text: Balthazar's Breakup -- The Dominos Effect 1 11/10/2008 2:36 PM PST BY TMZ STAFF He's gone from cavorting with half-naked Sienna Miller in Italy, to carrying a big pizza pie in L.A. with kids in tow. Balthazar Getty is now unencumbered -- except he's still married and very much financially on the hook. See Also Sienna Says Sayonara to B-Man


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That's my camper
Very nice house and good quality photo!
nice endroit
This place was fun, but it's closed up and gone now.
This appears to be the old Singletary Store. My family had a house called "Duck Pond" on Lake Moultrie back in the 50's near this store. We use to walk to the store for groceries.
I Like the photos of the site very much but I'm looking for information on a Soldier that was a Prisoner of the Civil War the Union. He is an Ancestor of mine and I was told he is buried there but in an unmarked grave due to being a Prisoner of War. I believe his name is Morgan Morris and I found this information a few years ago but lost it. So I was hoping someone could possibly help me again. I can be reached by email at firstname.lastname@example.com or email@example.com I check both of those weekly. If anyone can help me find my Great,Great Uncle I think that's what he is to me. My second Great grandparents son. So if anyone can help me please contact me. Thank you for your time. Mary Morris.
they did do a good job. Its been awhile since I posted anything hear and I never got involved with Zakk Barrons buisness...but i was truely saddend they let that house ruin. I havent any respect for that. It looks good...nice work. thanks SLomasney in Knoxvillle


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9/25/2016 | Walker gets win with heavy heart for Fernandez
Like the rest of Major League Baseball, Taijuan Walker competed with a heavy heart on Sunday, battling through a 4-3 win over the Twins just hours after learning that Marlins ace Jose Fernandez had died in a boating accident in Miami.
9/25/2016 | Mariners keep pace in WC race, beat Twins
Time may be running out on the Mariners playoff chances, but they kept hope alive with a 4-3 victory over the Twins on Sunday behind a trio of home runs by Nelson Cruz and Jesus Sucre at Target Field.
9/25/2016 | Cruz slugs 2 HRs, leaves with sore left wrist
Mariners slugger Nelson Cruz put the hurt on the Twins again in Sunday's 4-3 win with two more home runs, but had to leave the ballgame in the eighth inning after injuring his left wrist.
9/25/2016 | Umpire Layne leaves game with concussion-like symptoms
The first inning of the Twins' game against the Mariners was delayed after home-plate umpire Jerry Layne was hit in the facemask and left shoulder by a foul tip from Robinson Cano.
9/25/2016 | Cishek, Mariners reflect on life of Fernandez
Like the entire baseball world, the Mariners clubhouse was quieted Sunday morning by the shocking news of the death of Marlins pitching standout Jose Fernandez. And no one was hit harder then former Marlins closer Steve Cishek, who was a teammate and friend for the past five years.
9/24/2016 | Twins snap skid, slow Seattle's Wild Card chase
Other than a prodigious blast by Nelson Cruz, right-hander Tyler Duffey shut down the Mariners for seven innings Saturday as the Twins snapped a seven-game losing streak and dented Seattle's Wild Card pursuits with a 3-2 victory at Target Field.
9/24/2016 | Statcast of the Day: Cruz's mammoth blast
Nelson Cruz seems to be warming up for the stretch run, judging by his latest home run -- the second-longest blast in the Major Leagues this season, according to Statcast™ projections. Cruz launched a two-run shot a projected 493 feet into the upper deck at Target Field in the fourth inning of the Mariners' 3-2 loss to the Twins.
9/24/2016 | Walker, Santiago face off in Twins' last home game
With the Mariners still alive in the chase for an American League Wild Card spot, they'll turn to right-hander Taijuan Walker in the final game of a three-game series against the Twins on Sunday in the season finale at Target Field. Walker, who will start opposite lefty Hector Santiago, is looking to replicate his only previous outing at Target Field, when he threw a complete game and allowed just one hit -- a solo homer -- with one walk and 11 strikeouts on July 31 of last season.
9/24/2016 | Marte working hard to regain timing at plate
At first, Ketel Marte was just looking for the 22 pounds he lost while dealing with an untimely bout with mononucleosis. But now, the Mariners young shortstop is searching for the hitting stroke he seemed to misplace as well during his two-week stint on the disabled list last month.
9/24/2016 | Heart of lineup pounds away in blowout win
If the Mariners are going to do damage down the stretch, they're going to need their stars to lead the way. And the big boys -- Robinson Cano, Nelson Cruz and Kyle Seager -- certainly muscled up in a 10-1 win over the Twins on Friday as Seattle kicked off a critical season-ending road trip in fine fashion.
9/23/2016 | Paxton sharp as Mariners erupt to keep pace
Mariners lefty James Paxton took matters into his own hands on Friday with a powerful seven-inning outing, and he got plenty of help from his offense as Seattle topped the Twins, 10-1, to stay in pursuit of an American League Wild Card.
9/23/2016 | Mariners turn to rookie Miranda in Wild race
Rookie left-hander Ariel Miranda will make a critical start for the Mariners on Saturday against the Twins, who will turn to righty Tyler Duffey in the second game of the final 2016 series at Target Field.
9/23/2016 | Mariners hire director of baseball operations
Justin Hollander, the current director of player personnel with the Angels, has been hired as the Mariners' director of baseball operations, the club announced Friday.
9/23/2016 | Smith hitting September stride for Seattle
While much of the Mariners' offensive focus understandably circles around the heart-of-the-order trio of Robinson Cano, Nelson Cruz and Kyle Seager, veteran right fielder Seth Smith has quietly been playing a key role in the stretch run.
9/23/2016 | Start of Mariners-Twins delayed by rain
The Twins and Mariners opened Friday night's game (7:10 CT) in a rain delay, but were aiming for a 7:45 start.
9/22/2016 | Mariners disappointed in Clevenger for tweets
The Mariners issued a statement expressing their disappointment following a series of racially charged tweets by catcher Steve Clevenger on Thursday.
9/22/2016 | Mariners realize urgency of remaining series
Ten games. One road trip. One homestand. And a chance. That's what remains for the Mariners as them embark on their final trek of the season, with a three-game series against the Twins starting Friday, then three games at Houston and four final Safeco Field appearances against the A's.
9/21/2016 | King Felix silences invaders to his court
The King's Court was the smallest Felix Hernandez had ever seen it. A sea of Toronto blue pushed it back into just one small yellow triangle crammed behind the left-field foul pole. The King didn't like that.
9/21/2016 | Freeman's grab highlight for unexpected heroes
In a crucial game where the Mariners' big three of Robinson Cano, Nelson Cruz and Kyle Seager were a combined 0-for-12 until Cano's game-winning sacrifice fly in the 12th inning, a number of lesser-known heroes stepped up to facilitate Wednesday's 2-1 win over the Blue Jays at Safeco Field.
9/21/2016 | Cano delivers in 12th for Wild walk-off vs. Jays
Needing an ace performance to keep their playoff hopes alive, the Mariners got seven scoreless innings from Felix Hernandez on Wednesday and Robinson Cano drove in Guillermo Heredia with a walk-off sacrifice fly in the 12th as Seattle avoided being swept at Safeco Field with a dramatic 2-1 win over the Blue Jays.
9/21/2016 | Paxton, M's continue WC chase vs. Gibson
The Mariners are counting on this series with the Twins going better than their last meeting as Seattle battles to stay in contention for an American League Wild Card spot. They open the three-game series in Minnesota on Friday.
9/21/2016 | Mariners hope Cano gets rolling down stretch
One thing that would clearly help the Mariners as they head down the stretch is getting Robinson Cano rolling again. Manager Scott Servais acknowledged that the second baseman's 2-for-4 game with a two-run triple in Tuesday's 10-2 loss to the Blue Jays at Safeco Field was one of the few positives out of that setback.
9/21/2016 | Sanchez faces Felix as Blue Jays eye sweep
Mariners ace Felix Hernandez gets a second chance to face the Blue Jays in a meaningful game as Seattle tries to avoid being swept by American League Wild Card-leading Toronto on Wednesday at Safeco Field.
9/21/2016 | Mariners' small mistake paves way for Jays' big rally
The wheels came off for the Mariners in the fourth inning as nine straight Blue Jays reached base in an eight-run, eight-hit rally that knocked Hisashi Iwakuma out of the game and wobbled the Mariners' postseason hopes with what turned into a 10-2 loss at Safeco Field.
9/21/2016 | Blue Jays alone atop Wild Card after 4-homer rout
J.A. Happ became Toronto's first 20-game winner since 2008 on Tuesday night and delivered a blow to his former Mariners teammates' playoff chances in the process, while the Blue Jays smacked four home runs in a 10-2 runaway at Safeco Field.
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Effect of protein kinase A on calcium sensitivity of force and its sarcomere length dependence in human cardiomyocytes
Objective: We investigated whether the Frank–Starling mechanism is absent or preserved in end-stage failing human myocardium and if phosphorylation of contractile proteins modulates its magnitude through the sarcomere length-dependence of calcium sensitivity of isometric force development. Methods: The effect of phosphorylation of troponin I and C-protein by the catalytic subunit of protein kinase A (3 μg/ml; 40 min at 20°C) was studied in single Triton-skinned human cardiomyocytes isolated from donor and end-stage failing left ventricular myocardium at sarcomere lengths measured at rest of 1.8, 2.0 and 2.2 μm. Isometric force development was studied at various free-calcium concentrations before and after protein kinase A incubation at 15°C (pH 7.1). Results: Maximal isometric tension at 2.2 μm amounted to 39.6±10.4 and 33.7±3.5 kN/m2 in donor and end-stage failing cardiomyocytes, respectively. The midpoints of the calcium sensitivity curves (pCa50) of donor and end-stage failing hearts differed markedly at all sarcomere lengths (mean ΔpCa50=0.22). A reduction in sarcomere length from 2.2 to 1.8 μm caused reductions in maximum isometric force to 64% and 65% and in pCa50 by 0.10 and 0.08 pCa units in donor and failing cardiomyocytes, respectively. In donor tissue, the effect of protein kinase A treatment was rather small, while in end-stage failing myocardium it was much larger (ΔpCa50=0.24) irrespective of sarcomere length. Conclusions: The data obtained indicate that the Frank–Starling mechanism is preserved in end-stage failing myocardium and suggest that sarcomere length dependence of calcium sensitivity and the effects of phosphorylation of troponin I and C-protein are independent.
- Heart failure
- Contractile apparatus
- Contractile function
- Myocytes
- Protein kinases
- Protein phosphorylation
Time for primary review 21 days.
1 Introduction
The Frank–Starling law of the heart, which is based on the relations between sarcomere length, force development and its calcium sensitivity, indicates that an increase in diastolic filling causes an increase in peak systolic pressure. Conflicting results have been reported about the existence of the Frank–Starling mechanism in end-stage failing myocardium. According to Schwinger et al. [1] the Frank–Starling mechanism is absent in the end-stage failing heart, while Holubarsch et al. [2] and Vahl et al. [3] found that it was preserved in failing human myocardium. In the non-failing heart, several compensatory mechanisms exist to meet higher demands. An increase in heart rate will increase force development by increasing intracellular calcium [4], while activation of the sympathic nervous system increases pump function via β-adrenergic receptor stimulation. However, under pathological conditions these processes are impaired [4–6]. Hence, the Frank–Starling mechanism would be one of the few processes remaining to compensate for increases in workload.
Cardiac muscle normally functions between sarcomere lengths ranging from about 1.7 to 2.3 μm. Within this range, an increase in length results in an increase in force, which is due to the change in the overlap of actin and myosin as well as an increase in calcium sensitivity of force development. The increase in calcium sensitivity of force with increasing sarcomere length most probably results from an increase in calcium binding to troponin C [7,8]. However, the molecular basis of this length-dependent alteration in the affinity of troponin C for calcium is not completely clear. Evidence suggests that interfilament lattice spacing could be an important determinant of calcium sensitivity [9–11]. Because volume is constant, an increase in length is associated with a decrease in interfilament lattice spacing. The decrease in interfilament lattice spacing probably promotes formation of strongly-bound cross-bridges [12,13] which may enhance force production directly or indirectly via cooperative activation of the thin filament [14].
In addition, thin filament proteins other than troponin C (e.g. troponin I, troponin T, tropomyosin) influence cross-bridge binding or troponin C calcium binding and in this way might modify the length-dependence of activation [15]. Phosphorylation of troponin I and C-protein by the catalytic subunit of protein kinase A (PKA) causes a decrease in calcium sensitivity of isometric force production [16–18]. Phosphorylation of troponin I accelerates calcium removal from troponin C [19]. Furthermore, phosphorylation of troponin I and C-protein by isoproterenol may enhance the length-dependent change in troponin C calcium affinity [20]. If phosphorylation of troponin I and C-protein is involved in the length-dependence of calcium sensitivity, an explanation for the observed discrepancies concerning the Frank–Starling mechanism in failing human myocardium [1–3] might reside in different phosphorylation levels of the contractile proteins in failing human hearts studied by the different groups.
In the present study, we therefore investigated the effect of PKA incubation on force development in single human myocytes from donor and end-stage failing hearts at different sarcomere lengths (1.8, 2.0 and 2.2 μm). This approach allowed us to study intrinsic differences in length-dependent force development of the myofibrils and to establish if phosphorylation of troponin I and C-protein are involved in the length-dependence of calcium sensitivity. Cardiomyocytes were mechanically isolated from frozen human left ventricular tissue and permeabilised with Triton X-100. Permeabilised cardiomyocytes have the advantage that sarcomere length, isometric force development and its calcium sensitivity can be measured without interference of extracellular matrix components. Alterations in the extracellular matrix (e.g. collagen) that occur during heart failure may affect contractile properties of the myocardium. Furthermore, by removing all membranous structures (sarcoplasmic reticulum, mitochondria), myofibrillar contractile properties can be measured under standardized conditions (i.e. composition of the intracellular medium, sarcomere length) without disturbing factors present in the intact heart (i.e. hormonal factors, variable calcium concentrations).
2 Methods
2.1 Biopsies
Left ventricular biopsies were taken during heart transplantation surgery from three explanted failing hearts and from three donor hearts which were not used for transplantation for technical reasons. The patients were classified according to the New York Heart Association (NYHA) as NYHA class IV (end-stage heart failure). The characteristics of patients and donors are given in Table 1. The samples were obtained with approval of the local Ethical Committees. The investigation conforms with the principles outlined in the Declaration of Helsinki [21]. After excision the biopsies were transferred in cardioplegic solution and upon arrival in the laboratory, frozen and stored in liquid nitrogen for up to 7 years. Prior to the experiments, the tissue was stored at −80°C for up to one month.
|Donor 1
|Donor 2
|Donor 3
|Patient 1
|Patient 2
|Patient 3
↵a Abbreviations: AC=anticoagulant, ACE=ACE inhibitor, D=diuretics, N=nitrates, PI=positive inotrope.
2.2 Myocyte isolation and experimental set-up
The myocytes were mechanically isolated and mounted in the experimental set-up as described previously [22]. Briefly, a small piece of tissue (∼10 mg) was defrosted and kept on ice in 2 ml isolating solution which contained (mmol/l): free Mg2+ 1, KCl 145, EGTA 2, ATP 4, imidazole 10; pH adjusted to 7.0 with KOH. Subsequently, the tissue was cut into small pieces, put into a glass cylindrical beaker and mechanically disrupted with a Teflon piston within 5 to 10 s, using a tissue homogenizer set at 900 r.p.m. In this way, a suspension of small clumps of myocytes, single myocyte-sized preparations and cell fragments was obtained. To remove all membranous structures the cells were incubated in isolating solution containing 0.3% Triton X-100 for 5 min. Triton removes all soluble and membrane-bound kinases and phosphatases and thereby arrests the phosphorylation state of myofibrillar proteins. Thereafter, the myocytes were washed twice in isolating solution to remove Triton and kept at 0°C up to 24 h. Single myocyte-sized preparations were selected for mechanical measurements on the basis of size (100–150 μm long by 15–30 μm in diameter) and uniformity of striation pattern. The single myocyte was attached with silicon adhesive to thin stainless steel needles extending from a force transducer and a fixed bar while viewed (320× magnification) by an inverted microscope. Average sarcomere length was determined by means of a spatial Fourier transform [23] and adjusted to a sarcomere length of 1.8, 2.0 or 2.2 μm. Length and diameters of the cardiomyocytes were determined at a sarcomere length of 2.2 μm. Cross-sectional area was calculated assuming an elliptical cross-section.
2.3 Solutions
The relaxing and activating solutions used, contained, respectively (in mmol/l): MgCl2 6.42 and 6.28, Na2ATP 5.94 and 6.03, EGTA 5 and 0, Ca–EGTA 0 and 5. Ca–EGTA was made by dissolving equimolar amounts of CaCO3 and EGTA. In addition both solutions contained 14.5 mmol/l creatine phosphate and 60 mmol/l N,N-bis[2-hydroxyethyl]-2-aminoethane-sulphonic acid (pH adjusted to 7.1 with KOH). The ionic strength of the solutions was adjusted to 200 mmol/l with potassium propionate. The pCa (−log10[Ca2+]) of the relaxing solution and activating solution were, respectively, 9 and 4.5. The composition of the solutions was calculated by means of a computer program similar to that described by Fabiato [24]. The calculated free Mg2+ and MgATP concentrations were 1 and 5 mmol/l, respectively. Solutions with lower [Ca2+] were obtained by appropriate mixing of the activating and relaxing solutions, assuming an apparent stability constant of the Ca–EGTA complex of 106.45.
2.4 Force measurements
After curing of the glue for 50 min, the myocyte was transferred from the isolating solution on the mounting area to a small temperature-controlled well (volume 80 μl) containing relaxing solution. Isometric force was measured after the preparation was transferred, by moving the stage of the inverted microscope, to a temperature-controlled well containing activating solution. When steady tension was reached, the myocyte was returned to the relaxing solution. During the activation–relaxation cycles, the myocyte could be inspected through the glass bottom of the wells. All force measurements were performed at 15°C. The experimental temperature of 15°C was chosen to ensure stability of the preparation throughout the experiment. Moreover, at higher temperatures sarcomere uniformity during maximal force development is not well preserved [25]. Although maximal force is not very temperature-sensitive [26], caution should be exerted in extrapolation of the values found in this study to cardiac performance at body temperature. After the first activation at saturating (maximal) [Ca2+], sarcomere length was readjusted to the desired length (1.8, 2.0 or 2.2 μm), if necessary. The second measurement at pCa 4.5 was used to calculate maximal force per cross-sectional area. The next four to five measurements were carried out at submaximal [Ca2+] (pCa>4.5), followed by a control measurement at pCa 4.5. In two donor cardiomyocytes and four heart failure cardiomyocytes, a force–pCa curve was obtained at all sarcomere lengths (1.8, 2.0 and 2.2 μm), while in the other myocytes force measurements were performed at one or two different sarcomere lengths. After an initial series of force–pCa curves at different sarcomere lengths, the myocyte was incubated in relaxing solution containing the catalytic subunit of PKA (3 μg/ml: Sigma batch no. 35H9522) and 6 mM dithiothreitol for 40 min at 20°C. After PKA treatment, a second series of force–pCa curves was recorded. These force–pCa curves were obtained at sarcomere lengths of 1.8, 2.0 and 2.2 μm in, respectively, 7, 6 and 7 myocytes. On average, force decline in maximal force development after the first force–pCa curve measured at 2.2 μm for all cardiomyocytes (donor and heart failure) amounted to 2%. At the end of the experiment maximal force at 2.2 μm was on average reduced to 91±2%. Force decline during the entire experiment did not differ between donor and heart failure cardiomyocytes.
Passive force was recorded at a sarcomere length of 2.2 μm. It was obtained from the difference in force found when the myocyte was stretched from slack length corresponding to sarcomere length ∼1.7 to 2.2 μm.
2.5 Data analysis
The force–pCa relation was fit by a non-linear fit procedure to a modified Hill equation: where F is steady-state force. F0 denotes the steady isometric force at saturating Ca2+ concentration, nH represents the steepness of the relationship, and Ca50 (or pCa50) represents the [Ca2+] at which force=0.5×F0, i.e. the midpoint of the relation. Fmax, i.e. F0 at 2.2 μm sarcomere length, was determined from the second maximal activation at pCa 4.5.
Data points are given as means ±S.E.M. of n experiments. Differences were tested by means of Student's t-test.
3 Results
Isometric force and its calcium sensitivity were determined at different sarcomere lengths in eight myocytes isolated from three end-stage failing hearts and eleven myocytes from three donor hearts. Fig. 1 shows a ventricular cardiomyocyte from donor 2 when viewed in the mounting area at a sarcomere length of 1.98 μm (A) and 2.19 μm (B) in relaxing solution (pCa 9.0). Corresponding power spectra calculated from most of the cell visible by means of the spatial Fourier transform are shown in panels C and D. The half width of the power spectra is a measure of sarcomere non-uniformity within the preparation and corresponded to 0.02 μm in C and D. Average values for length, diameters and maximal force per cross-sectional area at a sarcomere length of 2.2 μm of failing and donor cardiomyocytes are given in Table 2. No significant differences were present between length, diameters and maximal isometric tension at 2.2 μm of the two groups. Passive force per cross-sectional area at a sarcomere length of 2.2 μm was low in both groups, albeit slightly higher in failing (2.4±0.3 kN/m2; n=8) compared to donor (1.3±0.2 kN/m2; n=6) myocytes (P<0.05).
|Length (μm)
|Width (μm)
|Depth (μm)
|Maximal tension (kN/m2)
|Donor (n=6)
|Heart failure (n=8)
3.1 Force measurements at different sarcomere lengths
Recordings of force production obtained during a contraction–relaxation cycle at sarcomere lengths of 1.8 and 2.2 μm measured at saturating and at submaximal [Ca2+] (pCa 4.5 and 5.0, respectively) are shown in Fig. 2. Force development was lower at 1.8 μm sarcomere length both at maximal and submaximal [Ca2+] compared to 2.2 μm. The sarcomere length-dependence of maximal isometric force and its calcium sensitivity were determined by exposing the cardiomyocytes to different [Ca2+] and measuring isometric force development at sarcomere lengths of 1.8, 2.0 and 2.2 μm. The force–pCa relationships obtained in myocytes from donor and end-stage failing hearts are shown in Fig. 3. Maximal isometric force development increased substantially with increasing sarcomere length (Table 3). Calcium responsiveness of force also increased with increasing sarcomere length in donor and failing cardiomyocytes. In both groups an increase in sarcomere length from 1.8 to 2.2 μm caused an increase in pCa50 by approximately 0.1 unit as illustrated by the dotted lines in Fig. 3. The steepness (nH) of the force–pCa relations shown in Fig. 3 did not differ between sarcomere lengths. The average values for pCa50 and nH are summarized in Table 3.
|1.8 μm
|2.0 μm
|2.2 μm
|0.64±0.12b (n=2)
|0.77±0.02b (n=4)
|1.0 (n=5)
|5.04±0.02b (n=5)
|5.12±0.01 (n=7)
|5.14±0.03 (n=5)
|3.76±0.28 (n=5)
|3.72±0.35 (n=7)
|3.65±0.44 (n=5)
|Heart failure
|0.65±0.03b (n=7)
|0.77±0.05b (n=4)
|1.0 (n=8)
|5.28±0.02bc (n=7)
|5.31±0.03c (n=4)
|5.36±0.02c (n=8)
|3.07±0.19 (n=7)
|3.09±0.43 (n=4)
|3.44±0.28 (n=8)
3.2 Donor versus failing cardiomyocytes
As can be seen in Table 3 calcium responsiveness of force was significantly higher in end-stage failing cardiomyocytes than in donor myocytes (P<0.01). At all sarcomere lengths the force–pCa curve of heart failure myocardium was shifted to the left compared to donor myocardium (mean ΔpCa50=0.22). The difference in calcium sensitivity at a sarcomere length of 2.2 μm is illustrated in Fig. 4. The steepness of the force–pCa curves, nH, did not differ significantly between donor and failing myocardium.
3.3 Effect of PKA on calcium sensitivity
To investigate if phosphorylation of the contractile proteins troponin I and C-protein are involved in the Frank–Starling mechanism, force–pCa relations were measured before and after PKA treatment at different sarcomere lengths. Recordings of force production before and after PKA treatment in a failing cardiomyocyte at a sarcomere length of 2.2 μm are shown in Fig. 5. PKA treatment did not significantly change maximal isometric force development at saturating [Ca2+] (pCa 4.5) in both donor and in failing cardiomyocytes. At submaximal [Ca2+], however, isometric force development after PKA treatment was significantly decreased (see pCa 5.2 in Fig. 5). A small non-significant decline in maximal force (6±2%) was seen which might be attributable to the duration of the incubations performed at 20°C.
The decrease in force at submaximal [Ca2+] reflects a decreased calcium sensitivity of force after PKA treatment. The PKA-induced shift in pCa50 in cardiomyocytes from failing hearts was almost identical at all sarcomere lengths (0.24–0.25 pCa unit, Fig. 6A). On the other hand, in donor cardiomyocytes PKA treatment caused only a minor non-significant shift in pCa50 (Fig. 6B), but the sarcomere length-dependent change in calcium sensitivity was preserved after incubation in PKA. Fig. 6B clearly illustrates that the difference in calcium sensitivity of force between donor and failing cardiomyocytes is abolished after PKA treatment. The values for pCa50 and nH at various sarcomere lengths obtained after PKA treatment are summarized in Table 4.
|1.8 μm
|2.0 μm
|2.2 μm
|5.03±0.02b (n=3)
|5.08±0.02 (n=4)
|5.14±0.03 (n=2)
|2.65±0.08 (n=3)
|2.58±0.22 (n=4)
|3.12±0.11 (n=2)
|Heart failure
|5.06±0.03 (n=4)
|5.11±0.06 (n=2)
|5.12±0.03 (n=5)
|3.85±0.45 (n=4)
|4.04±0.48 (n=2)
|3.61±0.36 (n=5)
4 Discussion
To study the force–length relation in human myocardium we have applied a previously developed technique using mechanically isolated single cardiomyocytes [25]. Control of the sarcomere length is of major concern when studying myofibrillar calcium responsiveness. A small decrease in sarcomere length of 0.07±0.01 μm, i.e. about 3% of the length of the preparation between the attachments was observed previously during maximal activation at a sarcomere length of 2.2 μm [27], which mainly originated from the compliance of the mechanical parts of the set-up [22]. This indicates that the sarcomere lengths during the activations in this study will be somewhat less than the nominal values determined in relaxing solution. However, the differences are similar in donor and failing cardiomyocytes.
It should be noted that the cardiomyocytes swell by removing the membranes, thereby increasing the interfilament lattice spacing. Since interfilament lattice spacing is an important determinant of calcium sensitivity [9–11], the values obtained for calcium sensitivity of force in this study may differ from those found in intact tissue. However, since donor and failing cardiomyocytes were treated equally, we do not expect that swelling interferes with the conclusions presented in this study.
In accordance with previous studies on human tissue no difference was observed between maximal isometric tension of donor and end-stage failing cardiomyocytes, whereas calcium sensitivity was significantly increased in failing myocardium compared to donor hearts [1,18,28]. Wolff et al. [18] suggested that the increased calcium responsiveness observed in failing myocardial tissue may be due to a reduction of the β-adrenergically mediated phosphorylation of troponin I and C-protein. In agreement with their study, our results indicate that PKA treatment of cardiomyocytes abolished the difference in calcium sensitivity of force between donor and failing myocytes at all sarcomere lengths. It should be noted that minor residual differences in calcium responsiveness due to changes in isoform composition (re-expression fetal troponin T isoforms [29–32], expression atrial light chain-1 [28]) and phosphorylation levels of other contractile proteins cannot be completely ruled out.
An increase in sarcomere length in cardiomyocytes from donor tissue resulted in an increase in maximal force development as well as in its calcium sensitivity. The increase in calcium sensitivity of force observed in human cardiomyocytes is consistent with previous findings in single cardiomyocytes from rat [10,14]. In addition, in agreement with these studies, sarcomere length did not affect the steepness of the force–pCa relationships.
Similar increases in maximal force and its calcium sensitivity were observed in cardiomyocytes isolated from end-stage failing myocardium. Hence, our results are in accordance with previous observations by Holubarsch et al. [2] and Vahl et al. [3] who found the Frank–Starling mechanism to be present in failing human myocardium. The change in calcium sensitivity in response to a change in sarcomere length was also found to be preserved in hypertrophied rat hearts using similar force measurements in enzymatically isolated single cardiomyocytes [23]. Schwinger et al. [1] did not observe an increase in force development after an increase of sarcomere length in failing myocardium, which suggested complete absence of the length-dependent force development in end-stage heart failure.
We hypothesized that a possible explanation for this discrepancy may be different phosphorylation levels of contractile proteins in failing myocardial tissue, since the phosphorylation level of contractile proteins affects calcium sensitivity of force development in myofibrils [16–18,33–35]. The phosphorylation level of contractile proteins may be altered in heart failure due to β-adrenergic desensitization resulting in decreased phosphorylation via PKA as discussed above or protein kinase C (PKC) [33,34]. The absence of desensitization in donor hearts might provide an explanation for the minor effect of PKA in donor tissue. Increased PKC activity has been observed in failing human myocardium [36]. As a consequence of altered PKA and PKC activity, resulting in variable phosphorylation levels of contractile proteins, the Frank–Starling mechanism may be masked in the end-stage failing myocardium. Based on our findings it appears unlikely that the different observations concerning the Frank–Starling mechanism in failing human myocardium [1–3] are due to differences in phosphorylation levels of troponin I and C-protein.
Komukai and Kurihara [20] observed that isoproterenol treatment of ferret papillary muscles enhanced the length-dependent change in calcium sensitivity of force. This observation suggests that phosphorylation of troponin I and C-protein may be involved in the length-dependent alteration in the affinity of troponin C for calcium. However, in our study, the length-dependent shift in calcium sensitivity was unchanged in both donor and failing cardiomyocytes after PKA incubation, indicating that PKA-mediated phosphorylation is not involved in the sarcomere length-dependent force development of the heart.
It is tempting to speculate that existence of the Frank–Starling mechanism may depend on variable, regional expression of fetal troponin T isoforms. Akella et al. [37] observed a larger increase in calcium sensitivity of force with an increase in sarcomere length from 1.9 to 2.4 μm in diabetic rat hearts re-expressing fetal troponin T than in control hearts. They envisaged that the modified troponin T could be incorporated preferentially in the part of the thin filament closest to the Z-line and that consequently, at longer sarcomere length, the unmodified complex would retain control of cross-bridge interaction. This would suggest that alterations in the troponin T isoform composition might influence the length-dependency of force development. In human end-stage failing hearts, Anderson et al. [29] observed re-expression of the fetal troponin T4 isoform in all cases, while others found increased troponin T4 levels in only half [30] or even 10% [31] of their failing samples. In contrast, Townsend [32] et al. observed an increase in fetal troponin T1, while Mesnard et al. [30] found decreased troponin T1 protein expression in failing ventricles. The ventricular samples used in our study proved to be uniform in troponin T composition by one-dimensional gel electrophoresis (data not shown). Hence, possible heterogeneity in troponin T isoform composition among failing human hearts and in its distribution inside the sarcomere might provide an explanation for the discrepancies concerning the length-dependent force development in human end-stage failing myocardium. It should be noted, however, that the findings of Akella et al. [37] would imply an enhancement of the Frank–Starling effect. Furthermore, the heterogeneous expression of troponin T might be a transient phenomenon in humans.
Some caution should be exerted in the interpretation of our findings. One donor and two heart failure patients received positive inotropic support (Table 1), which may have altered the phosphorylation status of myocardial contractile proteins. Therefore, effects of medication on our results cannot be completely ruled out. Furthermore, because donor tissue is scarce, the number of experiments on donor hearts is limited. In addition, other limitations inherent in human myocardial studies (variability in age, sex) apply. Nevertheless, this study shows clear differences between donor and failing heart, while the effects of PKA were studied within the same preparations.
In summary, our observations on donor and end-stage failing human cardiomyocytes indicate that the Frank–Starling mechanism is preserved in end-stage heart failure, suggesting that loss of the Frank–Starling mechanism does not contribute to the decreased cardiac performance in congestive heart failure. Other cellular mechanisms which may contribute to the dysfunction of failing myocardium involve alterations in calcium handling, contractile protein composition and extracellular matrix [38]. Furthermore, our results suggest that the length-dependent alterations in force development are independent of the degree of phosphorylation of troponin I and C-protein.
- Copyright © 2000, European Society of Cardiology


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2 Reviews
The taste was good, but my rhubarb never did seem to thicken up enough. I found the pie to be very watery and it ended up soaking the crust too much. I followed the recipe to the letter so I wonder if some of the measurements are off?
We loved this pie! I followed the instructions in the recipe, and was thrilled with the results. My rhubarb thickened very well, and I even used frozen rhubarb. Interestingly, the combination of rhubarb and raspberries reminded me of cherry pie. I'd definitely make this again! It was perfect with vanilla ice cream.


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February 11, 2016 by · Leave a Comment
Play Reading: "English Only" Coming to A Library Near You
Feb. 16, Feb. 17, & Feb 18 6pm—Play Reading: "English Only" Coming to A Library Near You. CTG's The Shop presents it's latest round of play readings... Read more »
Community Calendar: Feb. 11, 2016 – Feb. 17, 2016
Thursday, Feb. 11 4-5pm – Money Smart Workshop for Teens at City Terrace Library. Learn about credit cards, debit cards, interest rates, APRs, loans, savings and... Read more »
Community Calendar: Feb. 4, 2016 – Feb. 10, 2016
Saturday, Feb. 6 9am – South Coast Air Quality Management District Hearing on Exide Technologies. Public hearing will consider modification to Exide's Order... Read more »
Community Calendar: Jan. 28, 2016 – Feb. 3, 2016
Today, Thursday, Jan. 28 5pm – LA County Park Needs Assessment Workshop Jan. 28 at the Montebello Senior Center & Bell Gardens Veterans Park. Sessions are... Read more »
L.A. Ends Tax Licensing of 'Illegal Pot Shops'
The city will stop issuing new business tax certificates to medical marijuana dispensaries under an ordinance approved Tuesday by the Los Angeles City Council. Despite... Read more »
Community Calendar: Jan. 21, 2016 – Jan. 27, 2016
Today, Thurs. Jan. 21 5-7pm—Commerce Veterans Resource Center Grand Opening. The center will focus on providing information to reintegrate California veterans... Read more »
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Today, Thursday, Jan. 14 4-5:30pm–Personal Safety Seminar at City Terrace Library. Learn how to evaluate environments and react accordingly. Children's Rescue... Read more »
December 24, 2015 Issue
Community Calendar: Dec. 24, 2015 – Dec. 30, 2015
Today, Thursday, Dec. 24 10am-8pm – Holiday Ice Rink at Pershing Square Thru Jan. 18. Take to the ice and on select nights enjoy DJ nights, skating exhibitions,... Read more »
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Today, Thursday, Dec. 17 4-5pm – Holiday Storytime at Anthony Quinn Library. Enjoy an afternoon of stories, art activities, cake and a chance to take a picture... Read more »


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An interview with Tom Thorp of Mercury
Mercury began life as a quartet, formed…
Mercury began life as a quartet, formed…
What came first – the music or the misery? Pledge…More
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Phronesis are a jazz trio like no other, with an unfaltering command over style and tempo and a broad palette…More
Mammal Hands are a trio hailing from Norwich, signed with Gondwana Records. Drawing on influences from Steve Reich to Bonobo…More


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Fallopian tube
Staff Blogs
Vindication for Vancouver cancer prevention protocol: enthusiastic endorsement from study in a major medical journalBy Pamela Fayerman A BC innovation aimed at preventing ovarian cancer has not only been deemed safe by Italian researchers, but also worth copying around the world.
Staff Blogs
Fallopian tubes: breeding beds for babies AND ovarian cancer. Should they be removed for cancer ...By Pamela Fayerman As a proactive, preventive measure, Justine Greene had her Fallopian tubes removed after her mother died of ovarian cancer.


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Debbie Wasserman Schultz and Ted Deutch Happen to Get Money From SOPA Supporters
Believe it or not, South Florida Democratic Reps. Debbie Wasserman Schultz and Ted Deutch -- supporters of the Stop Online Piracy Act -- happened to get a lot of money from interest groups supporting the legislation.
According to the nonprofit, nonpartisan research organization MapLight, Wasserman Schultz and Deutch took in nearly $1 million combined in contributions from interest groups supporting SOPA, compared to only around $125,000 in contributions from interest groups not in favor of it.
SOPA and its Senate counterpart, the PROTECT IP Act (PIPA), were pretty much the talk of the nation yesterday, when several websites went down in protest of the potential for internet censorship that the bills' language carries.
It was apparently enough for Sen. Marco Rubio to change his stance yesterday, as the onetime cosponsor of PIPA said he changed his mind.
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Wasserman Schultz, a recipient of $569,428 in contributions from interest groups supporting SOPA, and Deutch, who took in $396,549, haven't changed their stances on supporting the legislation.
According to MapLight, Wasserman Schultz took in the 14th-most money from these interest groups out of the entire House of Representatives, and Deutch got the 34th-most.
Wasserman Schultz and Deutch -- the only two members of Florida delegation who are cosponsors of PIPA -- also received more money from those special interest groups than any other representative from Florida.
MapLight's numbers show that interest groups supporting the bill contributed about five times more money to House members than interest groups that oppose it -- more than $85 million compared to nearly $17 million.
Wasserman Schultz, who's also chairwoman of the Democratic National Committee, released an ambiguous statement through her press secretary yesterday not explaining specifically why she's supporting the legislation that's caused so much drama.
On the Senate side, Sen. Bill Nelson is still a cosponsor of PIPA and happened to rake in the 17th-most money in the Senate from interest groups supporting that legislation at $266,369.
You can find all this information from MapLight by clicking here for SOPA and here for PIPA.
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Susan Capell Sorey is a native of Midland, Texas. She currently resides in Midland with her husband. Hobbies include horse back riding, team roping, painting and writing children's books.
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Richard LaGarde, Injury Attorney, Raises Questions After Tragic Death of Texas Oil Worker
Houston, TX (Law Firm Newswire) May 6, 2014 - A Texas man was killed at a Rice Energy Inc. gas drilling site in Belmont County, Ohio.
David Zamora, 43, of Victoria, Texas was an employee of subcontractor Lee Specialties Ltd. He was crushed by a piece of heavy equipment on Saturday, April 5.
In its statement, Rice Energy did not explain what type of equipment had killed Zamora. No one else was injured. "Relatively speaking, oil and gas drilling is a dangerous occupation," said Houston personal injury attorney Richard LaGarde, who is not involved with the case. "Nevertheless, workers have the right to a reasonable level of safety at all times. Investigators have a lot of important questions to ask in an accident like this. Were all safety protocols properly observed prior to the accident? Was the subcontractor made aware of the specific hazards present at the job site? Was there a failure of equipment, and if so, was that equipment properly maintained?"
This is the first fatality for the natural gas industry in Belmont County. Rice Energy is nearing completion of its first Utica Shale gas well. It is also the first major incident at a Rice Energy site, according to a statement from Mike Lauderbaugh, the company's vice president of environmental health and safety.
Operations at the site have been suspended temporarily as the company and authorities investigate the accident. The company said the suspension was self-imposed and that when operations resume, they will be "conducted in the safest manner possible."
According to Charlie Dixon, the safety and workforce training administrator for the Ohio Oil and Gas Energy Education Program, the Ohio oil and gas industry had four fatalities in 2013, two of which occurred in driving accidents. And the Occupational Safety and Health Administration puts the industry's national death toll from 2003 to 2010 at 823.
"When accidents occur at work sites, you can't always count on corporate and government investigators to go digging and find out if there's more to the accident than meets the eye," LaGarde added. "I recommend that anyone whose family member was killed in an industrial accident speak with an experienced personal injury attorney."
LaGarde Law Firm, P.C
3000 Weslayan, Ste. 380
Houston, TX 77027
Phone: (713) 993-0660
Toll Free: 1-866-LAGARDE
LaGarde Law Firm, P.C.
Jason M. Welborn - Of Counsel
617 S. Buchanan Street
PO Box 2053
Lafayette, LA 70501
Phone: (337) 443-4100
Toll Free: 1-866-LAGARDE
- Nettles Files Reply Brief in Fun 5's Lawsuit Appeal in Dallas
Attorneys for Dawn Nettles have filed a Reply Brief on behalf of Ms. Nettles in her appeal of a Dallas trial court's ruling that GTECH enjoys "derivative immunity" for fraud lawsuits. A copy of Ms. Nettles' brief can be viewed by clicking on the link below: Nettles Reply Brief
- Plaintiffs and Hiatt Intervenors File Amended Pleadings
The Plaintiffs in the Fun 5's lottery game lawsuit against GTECH (International Game Technology) have filed their Fourth Amended Petition along with an Exhibit "A" which lists the names of the Plaintiffs who have sued GTECH. The Hiatt Intervenors have also filed a Second Amended Petition and 7th Supplemental Petition that lists the names of […]
- Plaintiffs File Appellee's Brief in Fun 5's Lawsuit
The Plaintiffs in the Fun 5's lawsuit against GTECH (International Game Technology), filed their Brief of Appellees in the Austin Court of Appeals yesterday. A copy of the brief can be read >>here<<.
- Representative of Governor Meets With Lottery Petitioner
The Petition Denise Deckard's parents purchased a Fun 's lottery ticket from the Texas Lottery Commission. They believed they had won a substantial cash prize based on the clear language of the ticket's instructions. However, when they attempted to cash the ticket they were informed that they were not winners. Denise felt this was fundamentally […]
- GTECH Files Motion for Summary Judgment in Fun 5's Case
GTECH (International Game Technology) has filed a Motion for Summary Judgment in the Fun 5's case pending in Austin. The motion alleges that there are elements to the Plaintiffs' causes of action that they will not be able to prove at the time of trial. GTECH has asked the court to hold a hearing on […]
See other news sources publishing this article. BETA | Tags: accident, Belmont County, oil and gas, personal injury attorney, Rice Energy, TX


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Where Purchase Your Pure Green Coffee Bean
When you are doing coffee roasting, you should also be very careful about the roasting opportunity. A person needs to know every single time a person end up being stop the roasting process, else he is going to burn the beans. Pay due importance to the changing color of this coffee beans when in order to roasting the beans. If you know the give an impression of roasted coffee, it will easier it is possible to understand need to stop the heating activity.
The greatest coffee beans are called Arabica. They come from a 'cherry' a lot more places grown on the tree to a high altitude from 4,000-6,000 feet. These trees are harvested with regard to their Green Coffee beans inside the cherry. Arabica trees aren't as plentifully full as Robusta . This is the reason Arabica coffee set in a premium price. Yes, quality gourmet coffee beans cost way more! Robusta is the lower quality bean. Should you buy whole bean coffee, there happens to be high probability that are generally buying premium Arabica secondary.
Once roasted, it's true flavor only lasts from about 1 week to the decision of three weeks depending upon the type of whole bean coffee you buy. And again, at a local grocery store, you don't know just how long that bag of beans has been in the shelf before buy it.
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In coffee, it can be seen in raw coffee beans that didn't been dried or stored properly. It can also be applied to warehoused coffee that already been stored for long periods associated with your.
Another detail in making a perfect cup of java that seems obvious is to use the proper amount of coffee--freshly ground, of path. Many of us are tempted to use a little upwards of is really necessary in our attempts at making the flawless cup of coffee. Coffee enthusiasts and coffee baristas alike agree that two tablespoons per four ounces water are every thing are needed.
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text:
The loop syntax of the template engine could be extended to allow a user to change the internal loop step from 1 to an arbitrary value. Ideally it would make it possible to output a loop in reverse by specifying a step of -1.
nicofuma added a comment -
It is covered by Twig (http://twig.sensiolabs.org/doc/tags/for.html http://twig.sensiolabs.org/doc/functions/range.html).
nicofuma added a comment - It is covered by Twig ( http://twig.sensiolabs.org/doc/tags/for.html http://twig.sensiolabs.org/doc/functions/range.html ).


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Hotels within 15 miles of Batangas
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"* You must always keep in mind this is the Philippines and certain luxuries come at a premium. You also need to keep in mind the quirks of being in a country like the Philippines. All things are relative when traveling. I live and work part of the year in the Philippines and Batangas is a grea..."
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Best Batangas Hotels
The colonial town of Taal has preserved its Spanish heritage buildings. The foremost of these structures is the Basilica de San Martin de Tours. First built in 1575, the basilica is one of the largest Catholic churches in the Philippines and Asia. It is important as the home of a 17th century image of the Virgin Mary called the Nuestra Señora de Casaysay. The basilica's bell tower is noteworthy as it is said to house the largest bell in the country. Taal volcano
A big attraction in Batangas is the active volcano island of Taal. Often compared to a Russian doll, this scenic volcano is located within an inland lake. Within the crater is a lake. Visiting the volcanic island is possible via boat. From here, visitors can trek up to the crater. Accommodation in the area includes the charming Club Balai Isabel in Talisay. Beaches and mountains
The dry summer months of April and May form part of the high season here as many people from the capital drive to Batangas's beaches. One popular beach town is Nasugbu, an area in the west with nice sandy beaches and a number of resorts. Nasugbu is also the site of a national park which is home to Mount Pico de Loro, a mountain that is popular with weekend trekkers and mountaineers alike. Those looking to stay in Nasugbu for the night can book a room at Canyon Cove Resort. South of Nasugbu is the peninsula of Calatagan, also a prime destination for those interested in beaches. Batangas's other peninsula, located east of Calatagan (Mabini Peninsula), is also a recommended destination for beach resorts. Anilao in Mabini is a great destination for diving and snorkelling.Eating and drinking and shopping nearbyDining in the restaurants of Batangas means savoring traditional foods in the Tagalog heartland. Taal Bayview Bistro, located in Taal town, features on its menu fried tawilis, a small freshwater fish lightly breaded and deep fried, and kalderetang kambing, which is goat casserole. Kilawin, a local type of ceviche, is another dish that is worth trying in Batangas's seafood restaurants. The commercial centres of Batangas city, the provincial capital, and that of Taal town are the best places to shop in Batangas. Visitors are encouraged to buy local snack souvenir items like macapuno (sweetened coconut) and panutsa (sweetened peanuts).Public transportAccess to Batangas is via two roads, depending on which part of the province you wish to visit. Those intending to go to Calamba, Lipa, and the coastal capital of Batangas city can take the South Luzon Expressway from Manila, the most convenient access route to the central and eastern portions of the province. Those heading to the beaches of Nasugbu and Calatagan in the west may use the Emilio Aguinaldo Highway which passes through Tagaytay city. Either way, the drive should not take more than three hours.


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NCAA tournament 2013 live chat
Scott Goldman, National Desk
on March 21, 2013 at 11:50 AM, updated
March 21, 2013 at 12:40 PM
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By Scott Goldman, National Desk
2013 NCAA Tournament
is underway, and we'll bring you live updates via Twitter, social media and our team of college basketball reporters around the country throughout the first two days of the tournament. Please join the conversation with your questions, or chat about your favorite teams — and we'll be monitoring the Twitter hashtag #marchmadness as well.
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|By Marketwired .
Article Rating:
|May 14, 2014 11:33 AM EDT
BEDFORD, MA -- (Marketwired) -- 05/14/14 -- EnterpriseDB (EDB), the leading worldwide provider of enterprise-class Postgres products and Oracle database compatibility solutions, today announced support for Postgres Plus Advanced Server on the OpenStack platform.
Support for EDB's flagship database on OpenStack dramatically expands the options for companies seeking a low-cost, enterprise-class relational database for cloud computing within a private cloud or on a hosted environment. Postgres Plus Advanced Server for OpenStack represents a portable and powerful relational database that can support 80 percent of the workloads most organizations run to support their operations.
"OpenStack has emerged as the de facto standard for companies running private clouds or tapping into public cloud environments and our customers want the option of using Postgres on this platform," said Ed Boyajian, CEO of EnterpriseDB. "As more enterprises integrate OpenStack into their IT environments for greater savings and flexibility, Postgres Plus on OpenStack will become the de facto alternative to costly, proprietary databases."
EDB is the largest Postgres software and services provider with enterprise-class software, professional services, support and training to ensure success with Postgres as organizations expand their deployments of open source software to the data center.
Connect with EnterpriseDB
Learn more about EnterpriseDB: http://www.enterprisedb.com
Read the blog: http://blogs.enterprisedb.com/
Follow us on Twitter: http://www.twitter.com/enterprisedb
Become a fan on Facebook: http://www.facebook.com/EnterpriseDB?ref=ts
Join us on Google+: https://plus.google.com/108046988421677398468
Connect on LinkedIn: http://www.linkedin.com/company/enterprisedb
About EnterpriseDB Corporation
EnterpriseDB is the leading worldwide provider of Postgres software and services that enable enterprises to reduce their reliance on costly proprietary solutions and slash their database spend by 80% or more. With powerful performance and security enhancements for PostgreSQL, sophisticated management tools for global deployments and Oracle compatibility, EnterpriseDB software supports both mission and non-mission critical enterprise applications. More than 2,400 enterprises, governments and other organizations worldwide use EnterpriseDB software, support, training and professional services to integrate open source software into their existing data infrastructures. Based in Bedford, MA, EnterpriseDB is backed by top-tier venture capitalists and strategic investors like Red Hat and IBM. For more information, please visit http://www.enterprisedb.com.
EnterpriseDB Media Contact:
Renee Deger
Corporate Public Relations Manager
Email Contact
If you had a chance to enter on the ground level of the largest e-commerce market in the world – would you? China is the world's most populated country with the second largest economy and the world's fastest growing market. It is estimated that by 2018 the Chinese market will be reaching over $30 billion in gaming revenue alone. Admittedly for a foreign company, doing business in China can be challenging. Often changing laws, administrative regulations and the often inscrutable Chinese Interne...
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So, you bought into the current machine learning craze and went on to collect millions/billions of records from this promising new data source. Now, what do you do with them? Too often, the abundance of data quickly turns into an abundance of problems. How do you extract that "magic essence" from your data without falling into the common pitfalls? In her session at @ThingsExpo, Natalia Ponomareva, Software Engineer at Google, provided tips on how to be successful in large scale machine learning...
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Why do your mobile transformations need to happen today? Mobile is the strategy that enterprise transformation centers on to drive customer engagement. In his general session at @ThingsExpo, Roger Woods, Director, Mobile Product & Strategy – Adobe Marketing Cloud, covered key IoT and mobile trends that are forcing mobile transformation, key components of a solid mobile strategy and explored how brands are effectively driving mobile change throughout the enterprise.
Sep. 29, 2016 03:45 PM EDT Reads: 2,171
In his session at @ThingsExpo, Kausik Sridharabalan, founder and CTO of Pulzze Systems, Inc., will focus on key challenges in building an Internet of Things solution infrastructure. He will shed light on efficient ways of defining interactions within IoT solutions, leading to cost and time reduction. He will also introduce ways to handle data and how one can develop IoT solutions that are lean, flexible and configurable, thus making IoT infrastructure agile and scalable.
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Data is an unusual currency; it is not restricted by the same transactional limitations as money or people. In fact, the more that you leverage your data across multiple business use cases, the more valuable it becomes to the organization. And the same can be said about the organization's analytics. In his session at 19th Cloud Expo, Bill Schmarzo, CTO for the Big Data Practice at EMC, will introduce a methodology for capturing, enriching and sharing data (and analytics) across the organizati...
Sep. 29, 2016 03:15 PM EDT Reads: 1,766
SYS-CON Events announced today that Bsquare has been named "Silver Sponsor" of SYS-CON's @ThingsExpo, which will take place on November 1–3, 2016, at the Santa Clara Convention Center in Santa Clara, CA. For more than two decades, Bsquare has helped its customers extract business value from a broad array of physical assets by making them intelligent, connecting them, and using the data they generate to optimize business processes.
Sep. 29, 2016 03:00 PM EDT Reads: 2,957
Internet of @ThingsExpo has announced today that Chris Matthieu has been named tech chair of Internet of @ThingsExpo 2016 Silicon Valley. The 6thInternet of @ThingsExpo will take place on November 1–3, 2016, at the Santa Clara Convention Center in Santa Clara, CA.
Sep. 29, 2016 03:00 PM EDT Reads: 2,757
Cloud computing is being adopted in one form or another by 94% of enterprises today. Tens of billions of new devices are being connected to The Internet of Things. And Big Data is driving this bus. An exponential increase is expected in the amount of information being processed, managed, analyzed, and acted upon by enterprise IT. This amazing is not part of some distant future - it is happening today. One report shows a 650% increase in enterprise data by 2020. Other estimates are even higher....
Sep. 29, 2016 02:00 PM EDT Reads: 4,172
A strange thing is happening along the way to the Internet of Things, namely far too many devices to work with and manage. It has become clear that we'll need much higher efficiency user experiences that can allow us to more easily and scalably work with the thousands of devices that will soon be in each of our lives. Enter the conversational interface revolution, combining bots we can literally talk with, gesture to, and even direct with our thoughts, with embedded artificial intelligence, wh...
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Video experiences should be unique and exciting! But that doesn't mean you need to patch all the pieces yourself. Users demand rich and engaging experiences and new ways to connect with you. But creating robust video applications at scale can be complicated, time-consuming and expensive. In his session at @ThingsExpo, Zohar Babin, Vice President of Platform, Ecosystem and Community at Kaltura, will discuss how VPaaS enables you to move fast, creating scalable video experiences that reach your...
Sep. 29, 2016 02:00 PM EDT Reads: 1,143
In his keynote at 18th Cloud Expo, Andrew Keys, Co-Founder of ConsenSys Enterprise, provided an overview of the evolution of the Internet and the Database and the future of their combination – the Blockchain. Andrew Keys is Co-Founder of ConsenSys Enterprise. He comes to ConsenSys Enterprise with capital markets, technology and entrepreneurial experience. Previously, he worked for UBS investment bank in equities analysis. Later, he was responsible for the creation and distribution of life sett...
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SYS-CON Events announced today that SoftLayer, an IBM Company, has been named "Gold Sponsor" of SYS-CON's 18th Cloud Expo, which will take place on June 7-9, 2016, at the Javits Center in New York, New York. SoftLayer, an IBM Company, provides cloud infrastructure as a service from a growing number of data centers and network points of presence around the world. SoftLayer's customers range from Web startups to global enterprises.
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19th Cloud Expo, taking place November 1-3, 2016, at the Santa Clara Convention Center in Santa Clara, CA, will feature technical sessions from a rock star conference faculty and the leading industry players in the world. Cloud computing is now being embraced by a majority of enterprises of all sizes. Yesterday's debate about public vs. private has transformed into the reality of hybrid cloud: a recent survey shows that 74% of enterprises have a hybrid cloud strategy. Meanwhile, 94% of enterpri...
Sep. 29, 2016 01:30 PM EDT Reads: 4,451
Businesses are struggling to manage the information flow and interactions between all of these new devices and things jumping on their network, and the apps and IT systems they control. The data businesses gather is only helpful if they can do something with it. In his session at @ThingsExpo, Chris Witeck, Principal Technology Strategist at Citrix, will discuss how different the impact of IoT will be for large businesses, expanding how IoT will allow large organizations to make their legacy ap...
Sep. 29, 2016 01:15 PM EDT Reads: 325
In his general session at 18th Cloud Expo, Lee Atchison, Principal Cloud Architect and Advocate at New Relic, discussed cloud as a 'better data center' and how it adds new capacity (faster) and improves application availability (redundancy). The cloud is a 'Dynamic Tool for Dynamic Apps' and resource allocation is an integral part of your application architecture, so use only the resources you need and allocate /de-allocate resources on the fly.
Sep. 29, 2016 01:15 PM EDT Reads: 2,923
SYS-CON Events announced today the Enterprise IoT Bootcamp, being held November 1-2, 2016, in conjunction with 19th Cloud Expo | @ThingsExpo at the Santa Clara Convention Center in Santa Clara, CA. Combined with real-world scenarios and use cases, the Enterprise IoT Bootcamp is not just based on presentations but with hands-on demos and detailed walkthroughs. We will introduce you to a variety of real world use cases prototyped using Arduino, Raspberry Pi, BeagleBone, Spark, and Intel Edison. Y...
Sep. 29, 2016 01:15 PM EDT Reads: 3,018
The vision of a connected smart home is becoming reality with the application of integrated wireless technologies in devices and appliances. The use of standardized and TCP/IP networked wireless technologies in line-powered and battery operated sensors and controls has led to the adoption of radios in the 2.4GHz band, including Wi-Fi, BT/BLE and 802.15.4 applied ZigBee and Thread. This is driving the need for robust wireless coexistence for multiple radios to ensure throughput performance and th...
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Internet of @ThingsExpo, taking place November 1-3, 2016, at the Santa Clara Convention Center in Santa Clara, CA, is co-located with 19th Cloud Expo and will feature technical sessions from a rock star conference faculty and the leading industry players in the world. The Internet of Things (IoT) is the most profound change in personal and enterprise IT since the creation of the Worldwide Web more than 20 years ago. All major researchers estimate there will be tens of billions devices - comp...
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The many IoT deployments around the world are busy integrating smart devices and sensors into their enterprise IT infrastructures. Yet all of this technology – and there are an amazing number of choices – is of no use without the software to gather, communicate, and analyze the new data flows. Without software, there is no IT. In this power panel at @ThingsExpo, moderated by Conference Chair Roger Strukhoff, panelists will look at the protocols that communicate data and the emerging data analy...
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Sep. 29, 2016 12:00 PM EDT Reads: 3,155


text:
in reply to I laughed, I cried, I...
=for later
wrote code...
There is no Extraterrestrial life
There aren't any suitably capable Extraterrestrials
Interstellar travel is too difficult
We're too uncool / not worth the trouble
What do you mean they haven't visited?
Other reason
Results (518 votes). Check out past polls.


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Adam Levine and Behati Prinsloo Share First Baby Photo!
Back on Wednesday, model Behati Prinsloo gave birth to a little baby girl, a precious daughter she shares with Adam Levine. Take a moment, and all together now: awwww!
They named the baby Dusty Rose Levine, a unique but not totally bizarre moniker for a kid, thank goodness.


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Interesting facts
- Elevated between 830 m and 1,215 m, the ski resort is among the 5 highest elevated ski resorts in the Czech Republic. The vertical drop from summit to base is 385 m. The average difference in altitude between base and summit of ski resorts in the Czech Republic is 253 m. Most runs are therefore relatively long.
- Snow coverage is usually best during March, offering an average snow depth of 60 cm at summit elevation and 28 cm at the base. Therefore Pec pod Snezkou is among the 5 ski resorts with best snow conditions in the Czech Republic.
- Offering 10 km of slopes and terrain, Pec pod Snezkou is among the 15 largest ski resorts in the Czech Republic.