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There are mornings when I wake up before my family, like to spend the quiet moments on the deck enjoying the stillness (these recent years with Ziggy, a beautiful friend who knows the value of quiet). We haven't had much winter in our town, don't know what that means to our farmers beyond hoping for a wet spring for all. As I drank my coffee on the deck this morning, it was not the winter chill that struck me (it is a little cool today, snowed a little last night, we used to call it a skiff). My thoughts today turned to the passage of time, and how we all treat tomorrow as a renewable resource—when in fact it is exactly the opposite.
Nail Yakupov delivered a wonderful performance on the Canadian prairies last night. The evening featured a goal, several excellent chances, intelligent decisions and miles and miles of miles and miles skating. For those of us who are Yakupov fans, and I assume that is everyone, it was a wonderful night. At 22, this splendid young man has invested most of four years of his life to our town, attempting to fulfill his dream. Proud, determined, gifted, he has attempted to grind his skills into something the coach can use, perceived as being not quite special, not quite good enough. Nail is part of the chorus, but never gets a solo, as every hockey man who has come to our town finds the same spot for him.
Moms and Dads the world over keep sending the Edmonton Oilers their children, and the Edmonton Oilers keep turning Jacks and Kings into sixes and sevens and nines. No matter what happens from here, Nail Yakupov is a King in my books. There is a goodness in him we can all see, an honorable and gentlemanly quality. The finest compliment you can give a parent is that you hope your children become just like their offspring. Such is the case with Nail Yakupov. Through four years of difficult times, he has maintained his good name in a town half a world away from the one he knows, working to find a better day. I believe that day will come in another town. I will be happy for Nail on the day he is traded, and will cheer for him loudly at every turn. This last decade of turmoil is not about these young men and their foibles, it is about the Edmonton Oilers and their inability to create an environment where these young men can flourish.
- Oilers in October 2014: 4-5-1
- Oilers in October 2015: 4-8-0
- Oilers in November 2014: 2-9-3
- Oilers in November 2015: 4-7-2
- Oilers in December 2014: 2-8-4
- Oilers in December 2015: 7-6-1
- Oilers in January 2015: 5-7-1
- Oilers in January 2016: 4-5-2
- Oilers in February 2015: 5-6-1
- Oilers in February 2016: 3-5-1
- Oilers after 59 in 2014-15: 17-32-10, 44 points (-61 GD)
- Oilers after 59 in 2015-16: 22-31-6, 50 points (-32 GD)
Things are getting interesting now in the spy vs. spy year over year race. Nelson's Oilers have been 10 points behind for much of the year but are now closing the gap. As Todd McLellan's chances of posting a second .500 month fade into black, Nelson's crew have begun to find something that rhymes. From here to the end of last season, Nelson and his men were 7-12-4—posting 18 points in 23 games. If McLellan's crew can equal it, they will finish with 29 wins and 68 points—seems high based on the GA we have seen this week.
McLellans main frustration tonight was with his defencemen being too soft in front of their own net, and dmen missing the net in o Zone.
— Ryan Rishaug (@TSNRyanRishaug) February 19, 2016
- Davidson—Clendening were successful at evens, and played a lot. Both men are rookies, and despite some wobbly bits (the EN goal was irritating, but not especially helpful to analyzing the evening), get a passing grade. They were with the Hall-Leon-Purcell line (Davidson 9-1) and got the puck up pretty well when they could control it and get away from the pressure. Brandon Davidson, at this point in his career, is playing brilliant NHL hockey.
- Sekera—Schultz also got the Corgi love, Schultz was soft on coverage on one of the goals (he needed to be more aggressive with the oncoming train, and let the goalie grab the puck). Sekera shows all the other men how to do it every game. Sees the open lane, makes a sturdy pass, follows up the play. Makes it look easy. Then he goes to the bench. Traitor. Schultz was fine, save for the GA where he was not effective in clearing the puck or tying up his man. Basic defense.
- Nurse—Fayne is a duo I think might make a good third-pairing someday, maybe next season. I liked Nurse's edge, and did not like his coverage in the slot. Rookies, even when the are bright and learning, can be really frustrating. Patience. Fayne remains the same, reliable, effective defensively and a welcome veteran in a season of rookie blue.
- Cam Talbot, after an extensive run of good-to-great, was not as sharp as he needs to be in order for his team to gain points. He would need a few of these in a month before I would feel a need to worry.
"We have to play with some authority. It can't be a freebie getting to the Oilers blue paint." – Oilers coach Todd McLellan
— Rob Tychkowski (@Sun_Tychkowski) February 19, 2016
The Edmonton Oilers had 16 high-danger scoring chances at 5×5 last night, double the Wild. They still lost, due to easy looks and loose morals around the net. Despite dangerous chances by Leon Draisaitl (4), Taylor Hall, Nail Yakupov, Connor McDavid and Darnell Nurse (2), Teddy Purcell, Jordan Eberle, Lauri Korpikoski and Benoit Pouliot (1), the club could not stop enough sorties or pucks. The power play rang and Nail hammered, but the Wild once again left Dodge City with two points.
- Leon Draisaitl and his line romped, but once again could not cash. I know the dice have no memory, but would bet we see a breakout from this trio soon, possibly tomorrow. The big man had more jump this game, possibly signalling recovery from those bumps and bruises collected on the road trip.
- Mark Letestu had so many chances on the power play it hurt. If one of those cashes, we are having a different conversation this morning. I like him, wish he had better mitts.
- Anton Lander had a reasonable night, he helps the PK to my eye despite the overall results on the PK last night. I don't see him getting any chances at all offensively, maybe I am missing them.
- Connor McDavid scored a goal, checked well and was responsible to my eye. A wonderful player, if they packaged his shifts into a 20-minute video I might just watch that.
- Hall—Purcell were dangerous all night long, I felt it was only a matter of time. Hall did score, but the Oilers got screwed out of a goal for the 90th time this year. Lordy. Anyway, hard-working line and they didn't get justice. Hall is pushing now, the line drives are finding leather, but this too shall pass.
- Pouliot—Eberle cashed early on a sweet goal but I felt they were chasing the puck a lot after that. The Koivu line did good work against this line, that is going to happen. Eberle is healthy now, you can see his quickness and passing ability give him an edge on most exchanges. Pouliot posted a solid game, good to see after a 24-hour cycle that saw some fairly pointed criticisms of the big man. Is on pace for a 50-point season, despite missing about 10 games. That has value, and as we talked yesterday, this player is bona fide and his efforts should be respected. If someone is dissing a player who brings real value, then I encourage you to assess the value of their opinion.
- Korpikosli—Yakupov was mostly Yakupov, that was his best game of the year. I counted four great chances (goal, pipe, two robberies) and he was as fast as I can recall him. Splendid game, I will hold on to that image and hope we see it when he is in Montreal (or wherever he ends up). That was the kind of effort I had hoped we would see under Todd McLellan, one hopes it is not too late while also knowing, in their heart, the die is cast.
- Hendricks—Pakarinen played the opposition to a standstill but didn't get a lot done offensively. The only line that did not have a dangerous chance, can't ask that from your 4line every night. I like both players, hope we see them on next year's team.
Janne Niinimaa. Once an Oiler, always an Oiler. Standing ovation. ? #NHLfi #Oilers pic.twitter.com/v5YMD4iPiA
— Iiro Harjula (@IiroHarjula) February 19, 2016
I loved Niinimaa. He gave it all for the Edmonton Oilers, bled copper and blue, sent gorgeous passes forward, played with creativity and imagination. In the history of the Edmonton Oilers, these boys from Finland keep capturing our hearts with their wonderful skills and fun-loving approach to life. I cannot imagine these years of being an Oilers fan without the presence of Janne Niinimaa and his countrymen. We miss you Janne Niinimaa, you were a splendid hockey player. The Oilers badly need another Niinimaa right bloody now.
McKenzie just said that Therrien wouldn't have said what he said without knowing his GM AND his core players back him up.
— TyggR (@akaRCN) February 19, 2016
Did the rounds to find out if Subban is on the market. One team executive said "his name has come up". @TVASports
— Louis Jean (@LouisJean_TVA) February 19, 2016
I want to post this before the trade happens (you get the feeling this thing won't take long) but my o my what an insane few days in Montreal. For the life of me I cannot begin to guess what is happening behind the scenes, but it has to be massive for this stuff to be reaching the media. I am struck by a few things:
- This doesn't happen to organizations that are well run, and the problem begins at the top. Chicago turned around in a heartbeat once Rocky Wirtz took over. If I owned the Habs, I would fire all of the executives before trading Subban, but this looks farther along than anyone outside realized.
- The Oilers are going to be in on this.
- Taylor Hall may be the ask.
- The teams may settle on something like Nuge and Nurse.
- The Habs might ask for Leon.
- I am in favor of acquiring Subban UNLESS the root of this issue with the Habs is catastrophic. I have no idea what the problem is, but Peter Chiarelli has to know the issue before dealing for him.
- If the due diligence returns a thumbs up on the issue, pull the damned trigger on the trade. This is too perfect for the Oilers. Expect an overpay, and that is the truth. They cannot let this impact defenseman slip through their fingers.
- Nuge, Nurse and Nail for Subban and Lars Eller. Does either side do this? No side? I am terrible at trade ideas so welcome your input.
- Things just got interesting.
McKenzie: "…And I've heard there maybe are a couple of teams in the Eastern Conference that have kicked tires on (Schultz)…" #Oilers
— Chris Nichols (@NicholsOnHockey) February 19, 2016
As is the case with Nail, probably the sooner the better. The Oilers wear this failure too, whatever their problems in turning prospects into useful players, the evidence suggests it is not getting better. I count Nail and Schultz among the Tambellini era failures, but an assist goes to MacT and it is disappointing to see that Todd McLellan was unable to unlock the defender. Not blaming the coach, but I had hoped there was something he could do to help 19.
A busy show, Friday edition starts at 10, TSN1260. We discussed Subban at length yesterday on the show, suspect it will dominant proceedings again today. Scheduled to appear:
- Steve Lansky, BigMouthSports. Subban on the block? Plus Flint and what is happening there.
- Antony Bent, FC Edmonton. Eddies training continues, they edge nearer their trip across the pond, and Spurs are kicking ass.
- Steve Kournianos, The Draft Analyst. Trying to get a feel for the available defensemen in this year's draft, and yes, I will ask about RH blue.
- Paul Almedia, SSE. Paul grew up a Habs fan, so this should be an interesting conversation in regard to Subban.
10-1260 text, @Lowetide on twitter. Amazing developments possible today.


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Phyllis Doyle
Recording Secretary
Phyllis Doyle is a retired sales and marketing agent who has held several sales and marketing positions with the latest being national sales manager at the Magnaflux division of Illinois Tool Works. She now stays involved in several volunteer activities. Aside from the PRCOrchestra Board, she volunteers for Holy Family Ministries and at Norwood Crossing Retirement Village. Phyllis also prides herself on being active in Edison Park Lutheran Church where she has held many leadership roles including Council President. Additionally, she runs several fundraising programs and is heavily involved in the music ministry at the Church. Phyllis lives in the Edison Park neighborhood of Chicago with her husband Jim and also spends much time enjoying being close to nature in Door County, WI.

subset: commoncrawl


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A Proper Craft Room2nd June 2010 | 2 Comments
I had always heard stories of people who had "Yarn Rooms" or "Craft Rooms" and I never really believed it were possible. I mean, who has that much extra space in their homes? Apparently more people that I would have imagined. But upon moving in with the boyfriend, and a couple of arguments over the […]
posted by admin
Tags: craft room, Crochet, cross stitch, knit, yarn
Filed under: Crafting


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Toy manufacturers urged to follow Lego's lead in producing disabled characters
Campaigners have urged more major toy manufacturers to make products featuring characters with disabilities after Lego bowed to pressure to include one in its new range.
Pictures of the plastic mini-figure of a young man using a wheelchair and apparently accompanied by an assistance dog were spotted at the Nuremberg toy fair in Germany and shared on websites devoted to the world's largest toy firm's products.
Lego confirmed that the wheelchair would form part of a set which would go on sale in June.
Journalist Rebecca Atkinson, who sparked a global campaign when she posted pictures of toys she had adapted with different disabilities on the internet, said it was a massive step towards ending "cultural marginalisation".
The mother of two, who is partially deaf and has tunnel vision due to genetic condition retinitis pigmentosa, established the #toylikeme movement to secure better representation of the 770,000 disabled children in the UK and 150 million across the globe.
It quickly gained tens of thousands of supporters on social media and resulted in her working as a creative disability consultant with Playmobil to work on adding characters to its range - with more than 20,000 people signing a petition urging Lego to follow suit.
The Danish firm had been criticised by the campaign for "pandering to disability stereotypes" because its only previous wheelchair-using character was an elderly man.
An online campaign via a Lego website for the creation of a Lego wheelchair skatepark was rejected on the basis that submissions with a "political agenda" would not be accepted.
"We are beyond happy right now," Ms Atkinson said.
"Lego have just rocked our brick-built world and made 150 million disabled kids, their mums, dads, pet dogs and hamsters very very happy.
"We're all conga-ing up and down the street chucking coloured bricks like confetti.
"But on a serious note, this move by Lego is massive in terms of ending cultural marginalisation, it will speak volumes to children, disabled or otherwise, the world over."
Ms Atkinson is now seeking investment via a crowdfunding website to grow the organisation and create an online hub to help parents find products which represent disability, and has raised £3,638 of a £16,000 target within just a few days.
A photograph of the figure - by the Promobricks blog - was featured on the BrickFans website which paid tribute to the campaign.
"For a number of months a social media campaign called Toys Like Me has called upon toy makers including Lego to start featuring more characters and toys that reflect real life a little more," it said.
"I'm sure you'll agree this is a great step in the right direction by The Lego Group. With Lego being the number one toy brand in the world right now, their products are greatly influential for its younger fan base.
"Providing an able bodied person with the notion that a disability isn't something to be frowned upon while also offering a young disabled person with a positive representation for them to project themselves onto during play, is an achievement which should be saluted."
Pasca Lane, head of PR at disability charity Scope, said: "Everything is awesome!
"Many parents tell us it is important for their children to have toys which they can identify with because it builds their confidence, self-esteem and the feeling of being included in society.
"It is great that Lego has responded to this demand and will go on sale in June. We hope this move will help build a better future and improve attitudes towards disabled children and their families.
"But too many toy manufacturers are still missing a trick by not making toys with impairments widely available. After all, the spending power of disabled consumers is worth over £200 billion."


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Drama, Attention........Cruelty....
Part 1
With Erin newly diagnosed with DID before she came here, I had asked her many questions trying to ascertain the stability of her internal system. Some might think the diagnosis itself would guarantee a state of upheaval but that is not always the case. There are no absolutes in the human psyche. For some this diagnosis provides much needed answers and it can actually provide relief and even an increase in stability. There are many high functioning people with DID.
Even knowing she had young alters didn't mean Erin was too messed up to be here. How Erin responded to her new diagnosis would depend on how honest she was both with herself and others.
Our conversations included alters and cooperation within her internal system and she acknowledged a need for toys for young children. She told me she wouldn't have enough room to bring all she might need because of luggage restrictions. I guess I thought the fact she was trying to accommodate these particular needs meant she was accepting her DID diagnosis but my assumption was not based on that fact alone. With my own experience I knew what to be looking for but Erin knew what to hide. Unfortunately, I would not get the real answers until after Erin was here.
When we talked about toys, I had told Erin I had plenty of them so I was sure she could find something suitable for her younger alters. Most of my collectible toys are stored in my barn loft with the boxes carefully stacked and covered with tarps to assure they stay protected and clean.
When Erin asked about the toys I told her where they were and that she could choose whatever she wanted to play with as long as she took good care of them and cleaned up after herself. She knew going in that these toys represent a considerable investment for me so it was important she treat them as such.
Erin came in from her search with some expensive, vintage toys. I was immediately taken aback knowing there were many, many toys that would have been more appropriate choices. Erin had to have done a thorough search to even locate these particular toys. I was concerned she seemed to have no regard for how much money I had tied up in these collectibles. All she saw were toys that were special to her so she wanted them despite the fact the represented an investment to me so additional wear would decrease their value. I never imagined she would help herself to so many or that she would choose such sought after toys. I had counted on some discretion and consideration from her.
I was not happy she had decided to take such advantage but I felt it was my fault. I had not set guidelines when telling her that she could play with some of my toys so I honored my word and I let her play with the toys she picked even though it was going to cost me more than I had anticipated or than I can afford. It did not occur to me if she had no consideration for my investment in these toys, that she probably had less for those still in the barn.
It wasn't until after finding what she had done with the brushes or some other big mess in my barn, that it occurred to me she could have done the same thing with the toys in the loft. If that was the case, there would be further financial repercussions for allowing her to go through those toys so I headed to the loft to see what I could salvage.
I didn't even get all the way up there when I spied the mess she had left. Boxes were strung around everywhere, on the stairs, in the rafters. The neat piles in the lift I had made to assure all of the toys were protected from dust, or even the roof leaks, were obliterated. The tarp that was supposed to be spread across the top and down the sides, as the final line of defense, was rolled back, completely out of the way.
There had been no attempt to pull the tarp back in place. Some boxes were still open. Lots of toys were exposed and filthy dirty and others were at risk from her inappropriate handling.
It was obvious Erin went through everything to see what was there and she had no qualms about pulling out many of most valuable item. She did not use the same thoroughness to assure all of these toys put away as protected as they were when she found them. It took me nearly two hours to clean up this awful mess and I am afraid to know what it cost me.
When I confronted Erin about this one, she made excuses claiming she had tried. The job she had done was the best she could do. This confrontation was the one that precipitated her desire to go for a walk so she could kill herself off of my property.
I know some of my readers think she was all about threats but this situation didn't feel like a threat to me. There were plenty of other times that we talked about her suicidal feelings that were much different from this day.
Much of Erin's time here what she wanted from me was attention......all the time.
On those days that Erin did go to the barn, she was continually running back to the house to talk to me. Her trips no more than 15 minutes apart. Even when I wrote down instructions she had to go over them everytime but there was never a change in the instructions or the horses' routine. Erin just wanted to be the center of my attention. She would even wake me to ask a question when she already had the answer. How do I know this? Because I would explain, she would tell me her way to do it and it never changed and she could easily repeat it to Dave or Lindsay without looking at the notes. Even Dave who is oblivious realized that Erin was seeking me out just for attention.
On the days she was too depressed to go to the barn, she would come in, flop in the chair and sigh until she got my attention. If I looked at her but didn't speak, she would leave for a few minutes and then yet again. This too
tended to be in 15 minute increments until I would finally give up and ask her what was going on. Then we would end up in what can best be described as therapy like sessions ending with her disclosure about wanting to die.
As a survivor of extreme childhood abuse who has done extensive work to heal, I understand the flawed thinking that keeps victims trapped. Over the years I have used those skills to help others. I believe this aspect of my life is a large part of what drew Erin to me in the first place those years ago.
Her efforts for attention designed to draw me into conversations like those on the phone when she first called me years ago. During these I addressed her flawed thinking, knowing it kept her trapped in darkness. Normally she would emerge from our talks lighter and she might even progress to happy and content but it never lasted long. Her perfectionistic views of how the world "should" be always led her to be disappointed. Then the spiral would start again. Erin thought it was anyone and everyone at fault but her, which is not anything she admitted before she came. It was a horrible cycle that seemed ongoing and it sure couldn't change when she refused any responsibility.
Without intervention, she just went farther and farther into the hole. Whether or not she would kill herself if left alone was beyond me. All I knew at first was that she was dealing with a crippling depression and she had history as a cutter. If or how we were affecting the downward spiral was not obvious early on, I knew she needed help but she told me she couldn't get it because she was out of state....and that she couldn't afford a ticket to leave until her next benefits check.
This was exhausting and I couldn't seem to get away from her until I finally resorted to locking myself in my room to get a break from her games. Until the day I confronted Erin about the toys, I hadn't seen the same threat she was serious about taking her life. Other days I worried about her depression and how much blacker it might get.....but on this day......I believed she meant to do it......and she meant it to cause me harm. Her body language, facial expression and the tone in her voice all said she wanted to die......and she wanted me to know it was my fault. There is nothing about such behavior that is typical. It takes a particular type of cruelty to make such a threat. The significance of it would escape me for some time.....but not forever. At least now.....Erin is gone....and she will never again be welcome here.
To be continued......
The Aftermath....


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John C H Spence
Elected in 2016
Elected in 2016
John Spence is internationally recognised and acclaimed for his contributions to the development and application of X-ray lasers to biology and molecular movies, to atomic-resolution electron microscopy, and to the development of new microscopies and spectroscopies which have given scientists new eyes to understand atomic processes in solids. By conceiving the diffraction-before-destruction X-ray laser experiments on protein nanocrystals, Spence and Chapman opened the way to a new damage-free method of protein crystallography. Spence's work with Zuo in electron diffraction has provided the clearest images of chemical bonds between atoms, which control the arrangement of atoms in matter, and so determine its properties.
© 2019 Australian Academy of Science


text: > Greetings. > > I am having issues with rpm/yum on a centos 5.2 x86_64. > > I am trying to update from 5.2 to 5.4. During yum update, the > application became unresponsive during the package search. It had not > begun to download any packages. > > I tried to do a "yum clean all", but that wouldn't complete either. I <snip> Odd thought: yum -y update yum ? mark


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Just came up with a gang sign for the masons.
maybe they've already thought of this one.. sweet tho.
Totally unrelated-
A few notes on the art of Figure Modeling!
In Chicago, IL, the going base rate for a FM is $15-20/hr. Sometimes with tips, as people may take photographs in order to reference the pose and finish the painting/drawing later. Again, this rate varies. Lots of models out there are working to raise it, and to see to better working conditions.
Visually, artists seem to prefer few tattoos & piercings and if you can SIT STILL, that's a big plus. Believe it or not, people are getting into this gig w/o much discipline so far as holding a pose goes. As well as staying awake! In addition, flexibility is helpful, altho' most artists don't necessarily want to draw you going thru your yoga routine. A no-brainer perhaps, based on the above stated- but get enough rest and an average amount of stretching and exercise.
Further points:
Hydration- Take a water bottle. Most places provide a heater/fan, but clean water may be hard to procure. Esp. if you have to use the bathroom on that precious 5-min break instead of searching for a cup. Pre-hydration is key for almost anything physical one could be doing.
Light snack- Recommendations include: nuts and raisins, fruit (dried or whole) and other granola/trail mix concoctions like energy bars and other not-so-messy hand-held foods that require little reheating or clean up.
Other- Take a robe for comfort (it can get pretty cold in some of these classrooms) as well as modesty, and reading material.
Having trouble with feeling faint or tired even though you've taken care of these things?-
Ask for a break: If you need it, the rest is well deserved and the artists will be accommodating. The hardest time to re-assume the pose is the 1st time getting back into it. So while you're sitting, memorize how your body feels against itself, and against the furniture. Try to steady your gaze at something. And you don't want to stare down the artists while they're studying you.
If you're holding a longer pose, most artists will "tape" you (altho' potentially not very carefully) in order to help you get back into the pose. The hardest time to do this seems to be when you must resume the pose after the first 25-30 minutes. Here's a hint- your head will go where your eyes do, so you can also re-assume a head position, difficult or easy, by closing one eye, then the other while looking down at the end of your nose and remembering what it falls against.
Also: Always anticipate the next pose: Even if you're holding one for the entire "session" (a word which can be used interchangeably to describe all or a portion of a sitting). This keeps you engaged and you can help yourself do this by looking at art both modern and classic. By increasing your exposure to and vocabulary for poses you simultaneously increase your own creative capacities.


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How Will The Event Planner Plan An Acrobatic Aerial Stunt Show?
by admin • June 20, 2018 • Event Planner Malaysia
Have you ever wondered how will it feel to walk on hands instead of legs? Or write using your toes instead of fingers? Probably no and this idea actually might sounds absurd to you, but not for those talented persons all across the globe who have devoted their lives to do something more motor!...Read more →


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Dear brothers and sisters,
If you have not already done so, please let us know if you plan to attend any of the missions. Note that we will be having a short 1-2 day community retreat before the start of each mission in each of the three locations.
Just a gentle reminder of the dates:
Minneapolis: April 2-April 10
Orange County, CA: April 16-April 24
Miami: April 30-May 8
Please note that we will confirm the exact dates of the community retreat, but for now please assume they will be 1-2 days prior to the start of the mission.
Please email me at firstname.lastname@example.com ASAP to know if you will attend: where you will attend: and how many you will be. If you will not attend any of the missions, there is no need to notify us.
God bless you and may these days leading up to Lent be fill your hearts with the desire to give and love with mercy.
Ale and David (MI)


text: A Romantic Garden Wedding in Georgia\\nAn antebellum mansion provides a romantic setting for one couple's elegant, early-spring celebration.\\nMike asked Jeanette to marry him in August 2008—seven years, seven months, and seven days after the couple began dating. \\"He proposed after we had cooked and eaten dinner together at home, just the two of us. It was perfect,\\" Jeanette says.\\n\\n\\n\\nJeanette wore a Paloma Blanca gown from Hannelore's Bridal Boutique, while Mike sported a Perry Ellis suit and a green tie.\\nThe couple married in the garden at Primrose Cottage, drawing on the antebellum mansion's classic design and incorporating a palette of slate blue and spring green.\\nThe bride carried a bouquet of roses, lisianthus, ranunculuses, with a hint of blue tweedia.\\nJeanette's bridesmaids donned crisp blue silk Watters dresses from Bridals By Lori.\\nThe Christian ceremony commenced at dusk under a simply decorated garden arbor with a reading of John Donne's poem \\"A Valediction: Forbidding Mourning.\\" Wil Parker from Mt. Bethel United Methodist Church officiated.\\nThe couple and their 100 guests then moved into the cottage's ballroom, where floor-to-ceiling windows overlooked the surrounding forest. To create an inviting space for the reception, Jeanette and Mike selected ivory damask tablecloths and alternating low and high centerpieces of white and green hydrangeas and ivory roses surrounded by votive candles. The floral designs were by Magic Moments at Primrose Cottage.\\nFor dinner, the couple offered a buffet of pasta and meat selections catered by the venue. \\"The pasta with wild mushrooms, sun-dried tomatoes, and spinach tossed in a goat cheese, white wine cream sauce was by far my favorite,\\" Jeanette says.\\n\\n\\n\\nThe three-tiered cake from Lulu's Bakery featured three flavor combinations: caramel cake with caramel filling, white cake with raspberry and white chocolate mousse, and chocolate cake filled with coffee ganache.\\nAfter a round of toasts, the newlyweds took to the dance floor.\\nFor their first dance, the newlyweds chose \\"La Vie en Rose\\" by Louis Armstrong. Entertainment was provided by The Moxie Band.\\nBut the band wasn't the only act. \\"Mike's brother, who recently placed third in the under-10 pianists' competition in Italy, gave a short concert,\\" Jeanette recalls. \\"And when we hit the dance floor later, he also revealed some impressive moves!\\"


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Vintage furniture has undoubtedly become an icon of industrial style furniture today. Not only are they cozy, contemporary and cool, these antiques with unique designs mirror the urban architecture and give a nod to heritage. Cheap Tolix Stool have managed to become people's favorites. You will spot them almost just anywhere; in restaurants, hospitals, outside on cafe terraces and public parks, offices, in the living room in homes, and kitchen areas as they are very versatile. Made from a metal sheet, these stools are light and easy to maintain.
The Tolix stools were designed in the early 1930s by a French designer Xavier Pauchard with an intention of providing a suitable seat for every worker at a local firm in France and slowly but surely found their way into homes and other spaces. He galvanized metal to create a rust-free metal. They come in a variety of colors or polished steel, multiple heights and can easily be stacked too, saving on space. The perforations on the sitting surface allow for water to drain when it rains, thus making them ideal for even outdoor spaces.
Industrial Style Furniture
When it comes to home furnishing in industrial style, the Silver Tolix Stool would make a preferable choice out of the other Tolix stool color range as they have a metallic tone that enhances any surroundings, whether one is looking forward to achieving a subtle look or a contemporary look. Leather chairs are also very synonymous when it comes to achieving an industrial look. The Leather Barcelona chair is rich in history; it was designed in 1929 for the Spanish royal family by a German designer named Ludwig Miesnvan der Rohe. Since 1953, however, it has been manufactured by knoll who is the licensed manufacturer and holder of all trademark rights. The chairs are made of leather cushions and crossed wielded stainless steel finished legs. They come in black, white, brown, tan and cream. The frames are made of massive suspension steel. For more information, visit us at Metro Furniture.
Office Chairs
Eames office chairs are widely recognized in the public and living spaces throughout the world. They are good statement makers oozing industrialism yet still very warm. They were designed in1958 by Charles and Ray Eames as an outdoor setting but are used mainly in contemporary interiors, including home offices, dining and living rooms. The chairs are available in fabric, vinyl or leather. Also equipped are innovative suspensions that create a firm, flexible sitting pocket and conforms to body shapes while still maintaining comfort. The chairs are made with aluminum frames and base for strength, yet these are light in weight and easy to move. They are also very earth friendly as they are made of 61% recycled materials.
Vintage furniture has proven to be very classy that oozes elegance and style. They are also very symbolic in the industrial look for interior spaces and outside spaces as they bring a touch of history and sophistication. Most of their prices, however, are high except for the Tolix stools which are a tad pocket-friendly. Visit us at http://www.metrofurniture.co.uk/tolix-stool-in-silver.html.


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ប្រធានបទ៖ ប្រព័ន្ធផ្សព្វផ្សាយព័ត៌មានជាសំឡេងសម្រាប់អង្គការសង្គមស៊ីវិល និងសហគ្រិនភាព
អំពីប្រធានបទ៖ IVR (Interactive Voice Response) is a technology that has been long used by organizations in developed countries to automatically respond phone calls and respond questions from user using pre-recorded messages, connecting users to a person if necessary, or to an answering machine where they can leave a voice message. Callers can select which information to listen to or which service they require by pressing numbers in the telephone's keypad, in response to instructions from the system (e.g., "please press 1 to know about out promotions, please press 2 to talk to the commercial department, please press three to…").
អំពីវាគ្មិន៖ Mr. Kheng Piseth is currently working as the Training Manager with the USAID-funded SPICE program, implemented by the Open Institute. The program facilitates social and business innovation using communications technology and improves communications in Khmer via mobile devices. The purpose of the program is to build on partnerships between technology-oriented civil society organizations (CSOs) and private sector entities to utilize existing technologies to promote and deliver a greater diversity of information to the public, improve communications in Khmer language using mobile devices, and increase the capacity of CSOs to use social media for development purposes.


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Production of a 360 video "through the eyes" of a festival goer at Igloofest, giving the viewer the opportunity to explore the festival as if he was there; content strategy for Tourism Montreal that will bring the tourists closer to the destination!
The 360 video is the future; it's an immersive experience that gives individuals the chance to have a 360 view of what they are watching. The VR360 is sort of like a panoramic photo, in video. The individual exposed to it can access to everything that is outside of the frame. There is no particular equipment needed, you only need a computer and you can move the image around with the help of the mouse, or simply watch it on your smartphone.
Igloofest / Piknic Electronik
" It was a real pleasure working with Tribu's dynamic team. Their expertise in virtual reality allowed us to make our first 360 video clip and position Montreal within this emerging trend in digital content." Tourism Montreal


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Hi! I'm Sue and I love reviewing different products that address issues that have either impacted me personally or my friends and family.
I don't know about you, but I've had more than one unhappy breakup in my life, and unfortunately so have a number of my friends. That's why, in this site, I take on T.W. Jackson's The Magic of Making Up eBook. While sometimes it's easy to move on from a relationship, at other times it's not so easy – nor is it easy to fully understand what the heck happened to begin with!
As you'll see from the review, ol' "T Dub" fully discloses that he isn't a counselor, but I like his common sense take on things, and so that's what intrigued me! Perhaps his insights will help you.
Enjoy the review, and thanks for stopping by!


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50 EUR pp
Single supplement: - EURREQUEST A QUOTATION
If you are tourist in Bucharest and you want to explore the city in a relaxing way, visiting the sites you cannot see from the car, the best way is to get our 3-4 hour cycling tour.
Our passionate guides will lead you through the stories of "Little Paris": Herastru Park, the Press House, Kiseleff Boulevard, the Arch of the Triumph, the Village Museum, the Peasant Museum, the Geology Museum, the Victory Square, the Roman Square, Aviators Square.
The bicycles are included, and you will receive a refreshment drink from us.
Group meeting in Charles de Gaulle square.
In the first part of the tour we will visit the largest park in Bucharest - Herastrau. You will discover a green area of the city, currently one of the most preferred destinations of the teenagers. We will visit a typical Romanian architecture church in Baneasa. Close to the little church there is the former Royal Train Station and Miorita fountain, which tells the story of Bucharest. The Press House is another objective to be visited during our cycling tour, before entering Kiseleff Boulevard, where we will pass near the Village Museum, the Arch of the Triumph, the Peasant Museum and the Geology Museum. We will cross Victory Square and we will arrive in the Roman Square for visiting a traditional bakery.
Back to Charles de Gaulle, we will pass near Aviators Memorial, but we will also stop for a refreshment drink to a relaxing terrace for more stories about the city.
End of tour.
Visited with the guide
Herastrau Park
St Nicolae – Baneasa Church
Mina Minovici historical House
The Royal Station
The Mass Media House
Kiseleff Avenue
The Arche of the Triumph
The Village Museum
The Peasant Museum
The Geology Museum
Victory Square
Roman Square
Traditional Romanian Bakery
Charles de Gaulle Sqare
Tour info
Duration: 3-4 hours
Departures: Every day, from March to November
Starting point: Charles de Gaulle Square
Tour specification
Price list
+6 pax .................................... 50 EUR
up to 6 pax.............................. 60 EUR
What is included
Professional English/ French/ German speaking guide
Bicycle rental
A drink from our part
What is not included
Photo and video inside the tourist objectives
Personal expenses, food and drinks at meals, less water
Price conditions:
Prices are per person
For groups of more than 10 participants, the price will be negotiated according with the number of participants
This tour is depending on the weather conditions


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Valletta, Malta's capital, is to be the European Capital of Culture in 2018, the European Commission has announced. Valletta is a UNESCO world heritage site. Not only is it one of the smallest capital cities in the world but with its 320 monuments, all within an area of 55 ha, Valletta is one of the most concentrated historic areas and popular heritage site in the world.
Want to read UNESCO Daily News Updates? Click Here!!!
The capital of MaltaThe capital of Malta is 'one of the rare urban inhabited sites that has preserved in near entirety its original features', according to UNESCO. Boasting a varied history, Valletta was ruled successively by the Phoenicians, Greeks, Carthaginians, Romans, Byzantines, Arabs and the Order of the Knights of St John.t
Androulla Vassiliou, the European Commissioner responsible for Education, Culture, Multilingualism and Youth, stated: "I congratulate Valletta on its successful bid. I am happy to see the enthusiasm generated in Malta for the European Capital of Culture title. I am confident that Valletta will develop an exciting programme of events with a strong European dimension and that the title can bring significant long-term cultural, economic and social benefits for the city and its surrounding area. I wish every success to Valletta."
Following Guimarães (Portugal) and Maribor (Slovenia) this year, Marseille (France) and Košice (Slovakia) will be European Capitals of Culture in 2013; Umeå (Sweden) and Riga (Latvia) in 2014, Mons (Belgium) and Plzen (Czech Republic) in 2015, Wroclaw (Poland) and Donastia-San Sebastián (Spain) in 2016. Aarhus (Denmark) and Paphos (Cyprus) have been proposed by the expert panel as European Capitals of Culture in 2017.
The Netherlands and Malta are the two Member States hosting a European Capital of Culture in 2018.
Browse All UNESCO World Heritage Sites in Malta.


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Moderators: GOLDEN-ARM, NJ Vike
There was some signs out on the N-S arterial (790?) where NYSW crosses to warn motorists that the crossing is now active.
Railhead wrote:Good Morning
The train just crossed French Road 11/11/2014 at 0930
lackman wrote:Congratulations !!!
Glad you got the photos you were looking for and cannot wait for the video. Post it on this web site as well please.
We moved to Ohio in 1972. When we went back to Utica for vacation for several days, I'd drive all around the Erie Lackawanna / NYSW in my free time hoping to see a train, any train. Ranged from Utica, up to Sherburne, and back. Usually would only see a box car or hopper car here or there. Usually headed back to Ohio with very little success.
Rail Pace Magazine kept me up to date with periodic reporting on the NYSW over the years, until I found this forum. The Utica related forums on this web site are priceless. I have been "there" on the west shore ROW and spent time at the hobby shop. Great picture. Keep up the good reporting. 4 box cars are better than none!!!!!!!!!!!
Best regards, and good hunting, Lackman
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- Research article
- Open Access
Interpretable correlation descriptors for quantitative structure-activity relationships
- Benson M Spowage1,
- Craig L Bruce1, 2 and
- Jonathan D Hirst1Email author
© Spowage et al; licensee BioMed Central Ltd. 2009
- Received: 5 November 2009
- Accepted: 24 December 2009
- Published: 24 December 2009
The topological maximum cross correlation (TMACC) descriptors are alignment-independent 2D descriptors for the derivation of QSARs. TMACC descriptors are generated using atomic properties determined by molecular topology. Previous validation (J Chem Inf Model 2007, 47: 626-634) of the TMACC descriptor suggests it is competitive with the current state of the art.
Here, we illustrate the interpretability of the TMACC descriptors, through the analysis of the QSARs of inhibitors of angiotensin converting enzyme (ACE) and dihydrofolate reductase (DHFR). In the case of the ACE inhibitors, the TMACC interpretation shows features specific to C-domain inhibition, which have not been explicitly identified in previous QSAR studies.
The TMACC interpretation can provide new insight into the structure-activity relationships studied. Freely available, open source software for generating the TMACC descriptors can be downloaded from http://comp.chem.nottingham.ac.uk.
- Angiotensin Converting Enzyme
- Partial Little Square
- Angiotensin Converting Enzyme Inhibitor
- QSAR Modelling
- Enalaprilat
Quantitative structure-activity relationship (QSAR) models correlate molecular chemical structure to biological activity. The underlying principle for QSAR modelling is the similar property principle: molecules with similar chemical structures will exhibit similar biological properties [1]. This principle can be explained by changes in chemical structure altering the electron distribution within a molecule, which is directly responsible for the activity of the molecule. QSARs can be used to elucidate a quantitative description of changes in biological activity arising from the exchange of the functional groups within a molecule. In general, QSAR modelling requires three main features: a data set of molecules, appropriate descriptors and an efficient statistical method for capturing correlation. Descriptors are characteristic properties of molecules, often represented as numerical values, which facilitate the analysis of chemical structure. A wide variety of molecular descriptors are available and descriptor selection is an integral process in QSAR modelling [2].
2D QSAR models are generated using descriptors derived from the two-dimensional graph representation of a molecule. In contrast, 3D QSAR models correlate activity with descriptors based on spatially localised features. Although 3D descriptors may allow more detailed descriptions of the molecular binding interactions between ligands and receptors, 3D methods are more time-consuming, due to the requirement of precise conformational detail on the molecule and exact alignment [3]. In some cases, 2D QSAR methods can classify the biological activity molecules more efficiently than some more complex 3D QSAR methods [4]. In many instances, the biologically active conformation of a molecule is unknown and 2D descriptors are useful, as they are not dependent upon spatial conformation.
Classic QSAR methods, developed by Hansch [5], provided a foundation on which numerous QSAR methods are now based: the correlation of physicochemical properties to activity using multivariable regression. Regression analysis models the activities of molecules through an equation constructed using a linear combination of physicochemical properties. The coefficient for each variable in the equation can, consequently, be examined to determine the extent to which each property contributes towards the activity of the molecule. Regression is central to many contemporary QSAR methods, although nowadays often the technique of partial least squares (PLS) [6] is used to cope with large numbers of descriptors. One of the appeals of regression is the relative ease with which models can be interpreted and this extends to approaches based on PLS [7]. Sometimes an interpretable model might be favoured over a more accurate, but less transparent, QSAR [8].
Over the last decade, advances in computational technology combined with contemporary methodologies have led to a vast array of new descriptors [2]. Topological maximum cross correlation (TMACC) descriptors were created [9] with the intention of developing an interpretable 2D descriptor for QSAR modelling. The TMACC descriptors are based on concepts derived from the grid-independent descriptors (GRIND) [10]. GRIND are alignment-independent 3D molecular descriptors which represent a molecule using a grid on which the product of pairs of force field interactions is plotted against the distances between the pairs [10]. This method is analogous to the autocorrelation descriptor, which represents atom pairs as a weighted histogram [11]. GRIND are interpretable, as only one value is stored for each distance range: the maximum product of the two force field interactions. This method was termed maximum auto- and cross-correlation (MACC) [10]. In a similar method, the TMACC descriptors use the topological bond distances and physicochemical properties of a molecule. Only the maximum value calculated as the product of pair combinations of physicochemical properties for each distance is used to generate the TMACC descriptors.
Previous validation of the TMACC descriptors was promising, with leave-one-out (LOO) cross-validated correlation coefficients comparable to those achieved by the state-of-the-art 2D QSAR method, hologram QSAR [9]. An external test set is often used to estimate predictive accuracy [12]. However, the external test set must be large to give results as reliable as cross validation [13–15]. We have previously shown [9], on the datasets in this study, that using a training/test set partition gives estimates of predictive accuracy that are qualitatively similar to those from cross validation. Thus, here we use cross validation only, as it makes more use of the data for model building. Whilst statistical validation is key, the interpretation and chemical significance of the structure-activity relationships generated are also important [2, 12]. To assess the interpretive ability of a QSAR model it is necessary to apply scientific rationale to the resultant interpretation [16]. Interpretation of the TMACC descriptors is achieved through analysis of the regression model generated by PLS. The predicted activity of a molecule can be attributed to specific atoms that contribute towards the TMACC descriptors. Visualization of the resultant atom activity contributions is accomplished by atomic colour coding based on sign and magnitude of partial activity.
The present study aims to evaluate the ability to identify known structure-activity relationships using the TMACC descriptors. To exemplify the TMACC descriptors, we investigate two datasets, which were previously used in a comprehensive comparison of modern QSAR approaches [17]. Models derived from the angiotensin converting enzyme (ACE) and dihydrofolate reductase (DHFR) inhibitor data sets were assessed to elucidate the encoded structure-activity relationships with the help of information in the literature and to evaluate the interpretive ability of TMACC models.
The data sets used in this study, 114 inhibitors of angiotensin converting enzyme [18] and 397 inhibitors of DHFR [17], have been widely used to investigate many QSAR methods [17]. Each data set contained experimentally determined activity (pIC50) values for each molecule. TMACC descriptors were generated using the topological data of each molecule. All nonpolar hydrogen atoms were removed and their atomic value added to the heavy atom to which they were bonded. Polar hydrogen atoms were considered explicitly. Physicochemical properties were then assigned to each atom. Four parameters were used to represent these properties: Gasteiger partial charges [19], logS parameters [20], Crippen-Wildman molar refractivity parameters [21] and Crippen-Wildman partition coefficient (logP) parameters [21]. Gasteiger partial charges were calculated using the method of partial equalization of orbital electronegativity [19]. This procedure calculates atomic charges in σ-bonded and non-conjugated π-systems using only the topology of a molecule. LogS parameters were used to describe atomic contributions to aqueous solubility [20]. Crippen-Wildman molar refractivity (MR) was used as a measure of the steric effect, which is determined through classification of atoms based on neighbouring atoms [21]. Crippen-Wildman partition coefficients (logP) are assigned to each atom as a measure of atomic lipophilicity, determined in the same way as Crippen-Wildman molar refractivity.
Properties used in generation of TMACC descriptors
Physicochemical property
Separate property
Gasteiger partial charge
Positive charge
Negative charge
(Solubility and solvation phenomena)
Positive logS
Negative logS
Crippen-Wildman logP (Hydrophobicity)
Positive logP
Negative logP
Crippen-Wildman Molar Refractivity
(Sterics and polarizability)
Molar refractivity
The activity bands used for TMACC descriptor interpretation
Very Positive
Very Negative
All calculations were performed using Nottingham Cheminformatics Workbench (NCW), a package which provides the function of generating the TMACC descriptors and the TMACC interpretation. NCW is a Java-based application, which is suitable for all major operating systems. It builds upon the original TMACC code (available from our website http://comp.chem.nottingham.ac.uk/download/tmacc). The original software only generates TMACC descriptors; there is no facility to interpret your model. NCW allows the user to start with a set of molecules and perform a full analysis upon them. The popular machine-learning workbench Weka is included to provide PLS modeling, as well as an in-house implementation. The in-house PLS algorithm was written before Weka included one. The results of the PLS analysis are used to determine the atomic contribution of each atom. The interpretation is visualized by a colour scheme depicting activity contribution by atom. The user is able to view molecules individually or tabulated. NCW will be available as open source software for download from our website, http://comp.chem.nottingham.ac.uk/download/ncw. NCW utilizes Marvin for drawing and manipulating chemical structures: Marvin 5.2.2, 2009 http://www.chemaxon.com. All molecular graphics were created using YASARA ("Yet Another Scientific Artificial Reality Application," http://www.yasara.com).
Results and Discussion
Angiotensin converting enzyme (ACE) inhibition
LOO cross-validation of the PLS models generated for the ACE and DHFR data sets gave q2 values of 0.70 and 0.53, respectively, consistent with those previously reported [9]. TMACC descriptors were generated for the ACE data set of 114 inhibitor molecules, previously used to assess the ability of a 3D QSAR method, comparative molecular field analysis (CoMFA) [18]. The data set contained a diverse range of structures and activities selected from literature [18]. ACE is a zinc metallopeptidase, which functions as a dipeptidyl carboxypeptidase, hydrolysing a range of oligopeptide substrates [22]. It acts to induce hypertension and is, consequently, a widely investigated target for antihypertensive drugs [23]. Several methods used to determine the ACE inhibitory activities (IC50 values) involved the use of the substrate hippuryl-histidyl-leucine (HHL) [24, 25]. An early method for determining ACE inhibitor activity was to measure the rate of hippuric acid production from HHL catalyzed by ACE [26]. However, it was subsequently discovered that HHL is a C-terminal domain specific substrate of ACE [27, 28]. Consequently, the structure-activity relationship shown by this data set is likely to reflect that of C-terminal domain specific ACE inhibition, rather than general ACE inhibition.
Frequency of activity of ACE inhibitor features as determined by the TMACC interpretation.
ACE inhibitor feature
C-terminal carboxylate carbonyl
C-terminal carboxylate hydroxyl
Central carbonyl
Zinc binding carboxylate - carbonyl
Zinc binding carboxylate - hydroxyl
Zinc binding sulfhydryl sulfur
Zinc binding phosphinate phosphorus
Zinc binding phosphinate carbonyl
Zinc binding phosphinate hydroxyl
P1' methyl
P1' lysyl nitrogen
An essential feature of any ACE inhibitor is a zinc coordinating group. The catalytic zinc ion is coordinated by three highly conserved residues present in both somatic ACE (sACE) domains [29]. The important functional role of the zinc ion in the active site domains of ACE has led to the development of peptide based inhibitors, such as enalaprilat, with additional zinc-binding functional groups, including thiol, carboxylate and phosphinate groups. The importance of zinc binding functional groups in ACE inhibition has been demonstrated in crystal structure and structure-activity studies [22, 30, 31].
Zinc binding groups were frequently recognized by the TMACC interpretation as positive for activity. All sulfhydryl sulfur atoms located in the optimal position for zinc-binding were identified as positive for activity. Analysis of phosphinate zinc binding groups showed all phosphorus atoms were identified as positive for activity. However, phosphinyl oxygen atoms were mostly shown as negative for activity. In contrast, the interpretation most frequently identified both carboxylate zinc binding group oxygen atoms to be positive for activity. Although the results do not fully capture the correlation between the type of zinc-ligand and inhibitor activity observed in structure-activity studies, (phosphinate > carboxylate > sulfhydryl) [18], perhaps the negative activity attributed to the phosphinate oxygen atoms reflects its weak zinc-binding ability in comparison to the other zinc binding groups.
The crystal structures of testicular ACE (tACE) in complex with various inhibitors (Figure 3) show the intermolecular interactions responsible for ACE inhibition in tACE and correspondingly the C-terminal domain of sACE [22, 30, 33]. In contrast to most zinc protease inhibitors, which primarily rely on the strength of their zinc binding groups for activity, domain-specific ACE inhibitors utilize weak zinc binding groups and exploit both primed and unprimed sides of the active site in order to mimic peptide substrates, thereby achieving domain selective inhibition [35]. Domain-specific inhibition of ACE is important, as each domain possesses individual functions [36]. This discovery has developed the number of applications of ACE inhibitors, extending from treating hypertension to protecting stem cells during chemotherapy [37]. A recent study has also suggested ACE may be involved in many physiological processes other than blood pressure regulation [38].
Conserved ACE residues important for inhibitor interactions
Functional interaction
C-domain residue
N-domain residue
Inhibitor carbonyl hydrogen bonding
Inhibitor carbonyl hydrogen bonding
Inhibitor carboxy terminal carboxylic ionic bonding
Inhibitor carboxy terminal carboxylic hydrogen bonding
Inhibitor carboxy terminal carboxylic hydrogen bonding
A C-terminal carboxylate is found in many ACE inhibitors. This feature interacts with several conserved residues in both domains of sACE, hydrogen bonding with tyrosine and glutamine residues, and also forms an electrostatic interaction with a lysine residue (Figure 3) [32]. Both C-terminal carboxylate oxygen atoms were identified as positive by the TMACC interpretation (Table 3).
Interestingly, the TMACC interpretation identified all inhibitor P1' lysyl nitrogen atoms as favourably contributing towards activity (Table 3). The interpretation also identified inhibitor P1' methyl groups as positive for activity. Thus, the TMACC interpretation identified P1' groups important for C-domain specific ACE inhibition, as illustrated in Figure 1. This C-domain specific bias in the data set, reflected by the TMACC interpretation, has not been shown in previous QSAR investigations using this data set [17, 18].
Dihydrofoloate reductase (DHFR) inhibition
Analysis of the TMACC interpretation of the DHFR data set.
DHFR inhibitor feature
2-amino nitrogen
4-amino nitrogen
C8 Quinazoline
N8 Pyrido [2,3-d]pyrimidine
Benzylmethoxy - methyl
Important human DHFR residues for inhibitor binding
Functional interaction
DHFR residue
2-amino hydrogen bonding
4-amino hydrogen bonding
4-amino hydrogen bonding
N1 hydrogen bonding
Pteridine ring hydrophobic interactions
Pteridine ring hydrophobic interactions
Pteridine ring hydrophobic interactions
Benzene ring hydrophobic interactions
Benzene ring hydrophobic interactions
Benzene ring hydrophobic interactions
Benzene ring hydrophobic interactions
5-methyl hydrophobic interactions
9-methyl and 10-methyl hydrophobic interactions
An important feature for DHFR inhibition is a 2,4-diamino-substituted pyrimidine ring [49]. The 2-amino and 4-amino groups form hydrogen bonds with highly conserved residues, which orientate the pteridine ring of the inhibitor accordingly. The orientation of inhibitor binding differs from natural folate binding. Although both involve 30Glu, the orientation of the inhibitor allows extensive hydrogen bonding with other DHFR residues, which is not possible in the folate binding orientation. Binding of inhibitors containing 2,4-diaminopyrimidine shows the 2-amino group forms a hydrogen bond with 30Glu [50]. Additionally, the 4-amino group of the inhibitor forms strong hydrogen bonds with the carbonyl groups of 7Ile and 115Val [46, 50]. The protonated form of N1 forms an electrostatic interaction with 30Glu [47, 51].
The N8 nitrogen of the pteridine ring forms a conserved network with a water molecule, which also hydrogen bonds with 30Glu and 24Trp [46, 52]. However, comparison of pyrido [2,3-d]pyrimidines and quinazolines suggests that the presence of the N8 hydrogen bond in inhibition by pyrido [2,3-d]pyrimidines may restrict the position of any bridge substituent, such as 9 or 10 methyl groups, preventing hydrophobic interaction of these features with the DHFR active site [53, 54]. Therefore, in general quinazoline DHFR inhibitors are more potent than pyrido [2,3-d] pyrimidine analogues.
The TMACC interpretation showed variable activity for the 2-amino group, with the activity approximately evenly distributed between negative and positive activity. However, interpretation of the 4-amino group showed a greater frequency of positive activity. The interpretation showed the N1 nitrogen as generally negative for activity. This classification could possibly result from the fact that the N1 was unprotonated within most molecules of the data set. However, studies suggest the protonated form of N1 forms a salt bridge with the DHFR active site [51, 55].
Comparison of the activity of C8 atoms in quinazoline inhibitors to N8 atoms in pyrido [2,3-d]pyrimidine inhibitors assigned by the TMACC interpretation showed the C8 atom of quinazoline inhibitors to be identified as positive for activity, whilst the N8 of pyrido [2,3-d]pyrimidines was most frequently negative for activity. This interpretation reflects experimental evidence, which indicates the presence of a C8 (quinazoline) is more potent for DHFR inhibition than an N8 (pyrido [2,3-d]pyrimidine) [56].
The presence of a 5-methyl group increases inhibitor potency by forming hydrophobic interactions with 115Val in human DHFR [53]. Methyl groups in the 9 and 10 positions of the bridge region also improve DHFR inhibitor potency, as the environment surrounding the bridge region is generally hydrophobic. Therefore, hydrophobic interactions with 22Leu may be formed by these groups [47]. The benzyl ring featured in many antifolate inhibitors forms hydrophobic contacts with many residues within the DHFR active site [46, 51]. This feature is often substituted for other aromatic rings and methoxy groups to increase hydrophobic interactions.
The TMACC interpretation identified 5-methyl groups as positive for activity, consistent with experimental data, which suggests this feature is important for the inhibition of human DHFR. The interpretation also identified methyl groups in the 9 and 10 positions as positive for activity. This is consistent with the known hydrophobic interactions formed by these features within the DHFR active site [47]. The TMACC interpretation identified the methyl of methoxybenzyl groups substituted around the benzoic acid moiety of inhibitor molecules as positive for activity. This classification is supported by the hydrophobic interactions in which methoxy groups have been shown to participate within the DHFR active site [46, 51]. The TMACC interpretation of the DHFR data set identified many key structural features for DHFR inhibition. The analysis suggests that the hydrophobic groups investigated were more frequently identified as positive for activity than the hydrogen bonding groups investigated (Figure 6).
Analyses of the TMACC QSARs modelled for the ACE and DHFR data sets have shown that the TMACC interpretation can identify distinctive features of a structure-activity relationship. The TMACC interpretation provided a clear and precise representation of the activity of specific groups. Amalgamation of the atomic activity values determined for such groups within a data set, showed strong correlation with experimental evidence, which shows the TMACC interpretation can produce models which accurately depict the features of a structure-activity relationship.
Overall, the TMACC interpretation modelled the ACE inhibitor structure-activity relationship highlighted important features for C-domain selective ACE inhibition. The TMACC interpretation provided a consistent representation of the structure-activity relationship present in the ACE data set. However, the insight into the structure-activity relationship of ACE inhibitors produced by the TMACC interpretation was limited by the size of the data set. To obtain a more detailed analysis of components important or detrimental to the ACE inhibitor structure-activity relationship, it would be necessary to investigate a data set which represents a comprehensive range of functional groups and structural components. Investigation of the activity of features important for C-terminal domain selective inhibition in comparison to features important for N-terminal domain selective inhibition would provide further insight into the interpretive ability of the TMACC descriptors.
An inherent weakness, due to the 2D nature of the TMACC descriptor, is insensitivity to chirality. However, the use of chirality descriptors derived from topological data may provide a solution to this limitation and may also improve the predictive ability of the QSAR models [57]. Investigation of alternative or additional atomic properties used in the TMACC descriptor would provide an insight into the properties which contribute towards activity. The effect of implementing more sophisticated partial charge calculations would be interesting, as a recent study has suggested that the method used for partial charge calculations can affect QSAR predictive accuracy [58]. Investigation of a wider range of data sets would provide further validation of the utility of the TMACC interpretation.
We thank GSK for partial funding of a PhD studentship for CLB. We thank Abrar Hussain for technical assistance and helpful discussion. We thank James Melville for the development of the TMACC descriptors and related software. We thank ChemAxon for a license for Marvin.
Authors' Affiliations
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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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Monday, May 04, 2009
Putting the Web in Web Applications
When we set out to build 280 Slides, we wanted to create an application that made no concessions: something that felt as interactive as the desktop experience, while leveraging all the benefits of being online. We coined the term "desktop-class applications" as a way to describe our vision for what web apps should be. We also knew it wasn't enough to just recreate a desktop presentation tool pixel for pixel. We wanted to do something new, and to truly take advantage of being a web based solution.
The key to having a great presentation is having great media. A picture that helps tell the story with infinitely more clarity, or that just helps tell a good joke. A movie that shows a demo of your cool new widget that everyone's going to buy. Not all presentations, and not all individual slides will work this way, but the kind of in-person, captivating speech that Steve Jobs would enjoy relies almost entirely on images. And, of course, an engaging presenter.
So, if having great media is key to having a great presentation, it's important to be able to find great media for your presentation. Not all of us have an art department on hand, so we made this idea central to 280 Slides, and we did it with a lot of help from Google APIs.
If you take a look at what we call the Media inspector, you'll see we have top level choices for pictures, movies, and shapes. Both the pictures and movies tabs let you search popular web services to find the perfect media for your presentation.
We're excited about finding other ways to integrate with Google services as well. For example, we hope to eventually enable publishing a presentation directly to YouTube, and use Google to log in to our service rather than having to create a new username.
We're also planning on changing the way we interact with the Google APIs. In addition to 280 Slides, our company makes a web application framework called Cappuccino. The media integration in 280 Slides has been a huge hit with our users, so we plan to build this feature directly into Cappuccino and let anyone building a web app integrate media searching with little effort. This means changing our approach from server-side to client side aggregation using JSONP. The AJAX APIs, YouTube APIs, and all the other APIs we use are now available by using JSON with padding. JSONP lets us work around the browser's same-origin policy to better integrate with third-party web services without proxying through a server.
280 North is going to be at Google I/O on May 27-28 to show off 280 Slides and how we integrate with the Google APIs. We'll also be showing off the beginnings of integrating this in Cappuccino which should be interesting to JavaScript developers. We hope you'll stop by the Sandbox!
If you want to learn more about how 280 Slides uses Google APIs, check out these Google Code videos with one of the co-founders:
3 comments:
I want to use the API Search AJAX, to removing results for the search query (Non-Javascript Environments).ReplyDelete
The TOS allow it?
My name is Rajarshi Chakraborty, and I am Vice President of Innovation Systems Private Limited, web design and software development Company. We specialize on all areas of custom software development, complete website solution and E-commerce.
I invite you to look over our portfolio of latest web development projects.
http://www.invspl.com/portfolio/ or http://www.invsl.com/portfolio.html/
We also work using Elance.com, Getacoder.com, Getafreelancer.com and Guru.com
We're looking for business partners who fit in one of the following criterion:
1. Business consultants who can refer one or more software project(s) to us and earn a percentage of the project(s) revenue.
2. Individuals who are in charge of purchasing or outsourcing software development for an established organization.
3. Software development companies who look to outsource their software development work.
We offer either revenue share or commission based packages for the above eligible candidates
We are open to discuss with any further business possibilities.
Looking forward to your reply,
For Innovation Systems Private Limited.
Rajarshi Chakraborty.
Vice President.
Software Research & Development Centre.
203, Sarat Bose Road.
Phone: +91.33.40089512 / +91.33.40089511
Mobile: +91.9830970585 / +91.9231800482
Email: firstname.lastname@example.com / email@example.com
Website: www.invspl.com / www.invsl.com
- Anonymous5/14/2009 6:24 AM
This comment has been removed by a blog administrator.ReplyDelete


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This Week in Science
Please bear in mind that these are all simply headlines. Please READ the articles linked above before commenting on any of these stories, as a one sentence summary does not present all the facts.
Test tube baby: http://bit.ly/13V60OO
Artificial heart: http://nyti.ms/18WdNxW
Exoplanet: http://bbc.in/13DOAHB
Planarian worms: http://bit.ly/1b1onEu
Gene therapy: http://bit.ly/16xDZZt
Star birth: http://bit.ly/130nzX4
Reproduced from the IFLS site on Facebook.
Click it. Like it. Love it!


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Mr. Canada Post brought in a box from Offhand Designs today. Meet Patty and Snoopy.
Kazul is now available with a few fresh changes... in a splendid array of treasured textiles inspired by the times and trends of the Californian Classic Charlie Brown. The bag features a front ZIPPER pocket for I-pad, magazine or pattern below! Kazul opens up wide with a stay-put 16" x 11" doctor's bag frame and another, deep pattern or I-pad pocket on the inside of the bag, as well as our traditional zipper pocket, pouches and pockets! Rolled leather handles and a matching leather flap finish the look beautifully!
Capacious carry-all with 3 compartments and endless pockets, pouches and tool slots. Room for all of your electronics, books and the central compartment pops open and stays open with a practical hex-frame closure for knitting or just seeing deep into the corners. Versatile handles offer short handles and a luxurious adjustable shoulder strap which extends to wear cross body for heavy lifting.
Are you ready for Ambah's Mystery KAL?
When will the first Clue be available in my timezone?This is awesome. We don't have to wait until Friday to start.
This link shows the day/ time in different parts of the world for the first clue release.
Did you know there are prizes?
5 Silver "ambah" shawl pins: 5 winners will be randomly drawn from the FO thread and announced March 22, 2017We're picking my dad up at the airport tonight. He's been in Honduras for the past 10 days on his annual mission trip. He'll be tired and hungry and sore. He'll tell us it's his last trip. And then when they start talking about the next trip in a few months he'll be signing up again :)


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When reconditioning an existing system, Bondtech uses the most advanced technology to bring the autoclave up to today's standards. When the autoclave is completed, the unit will not only look like new, but it will also perform and last like a new unit. When refurbishing a unit, we will take into consideration our customer's unique requirements as well as budget considerations.
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"Veganism is a way of living which seeks to exclude all forms of exploitation of, and cruelty to, animals for food, clothing or any other purpose."-Vegan Society
Why go vegan?
- For your health
- For the environment
- For animals
The above reasons don't necessarily fall in that order for each person. For example, I personally started to eat more plant-based foods for my health. My motivation to eat more plant-based started with health, but became more ethically-driven as I watched more undercover videos and documentaries about the factory farm industry. I couldn't believe what I did not know for most of my life! As I learned more about what happens in factory farms, my plant-based conviction grew even stronger. There is also huge impact on the environment when choosing plant-based. I call these three key points the triangle effect of plant-based eating. You are significantly helping three areas when you choose to incorporate more veggies: yourself, the planet and animals.
What are your personal motivations for incorporating more plant-based foods into your diet?
I use the word plant-based because sometimes the 'v' word labels and isolates vegans, creating a separation of 'us and them'. When there are no labels associated with eating more plant-based foods (similar to diet labeling, which I do not believe in) it's easier to transition into a plant-based lifestyle by doing what's best for you. Perhaps you are making Meatless Monday your plant-based day or incorporating one plant-based meal a day. Whatever steps you are taking towards plant-based, be it small or large, it's all good! Don't feel like you need to jump in with both feet or that it's all or nothing. Small steps are actually big steps!
Once you start incorporating more plants into your life you will notice a few things about your health:
- radiating skin
- brighter eyes
- more energy
- clear focus
- better concentration
- lower cholesterol
- decrease blood pressure
- feeling happier
- stronger bones
- less anxiety
- and many more!
We will continue to highlight the benefits of plant-based eating on our blog and through social media. Make sure to follow us for tips, recipes and inspiration. And, please let us know your thoughts, questions and feedback through email or comments. We want to be on the plant-based journey with you and hear how it's positively affecting your lifestyle.
Here's to new beginnings and a healthy YOU!


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This episode we cover some more news, both good and potentially bad, before discussing issue 3 of the iZombie comic. So far we have been enjoying what we've read so will this continue the streak? Find out in this episode.
And as always thank you for listening to iZombie Radio.
When the news/episode breaks, be sure to tune-in here or our website at www.izombieradio.com. Be sure to follow the podcast on twitter @iZombieRadio or at www.facebook.com/izombieradio. If you have any questions, comments, or feedback; feel free to email us at email@example.com. Be sure to subscribe to us on iTunes, please rate and review us there, and we are also on Stitcher, Tunein Radio, and Google Play so be sure to check us out there as well! Also be sure to follow us, the hosts of iZombie Radio on Twitter.
Chris King: @CKinger13
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We are also a part of the DCTV Podcast Network of podcasts. There you can find podcasts on other DCTV shows like The Flash, Arrow, Supergirl, Legends of Tomorrow, Gotham, Classic DCTV Shows, Black Lightning, Krypton, and now Titans! Check us out at www.DCTVpodcasts.com where you can find each individual podcast or subscribe to our mega feed!