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Category Archives: Miscellaneous
The 4 Most Unanswered Questions about Fences
Important Facts You Should Know About High Security Fencing
The safety and protected of your family will be guaranteed once you install high security fences. Every homeowner has their own belongings and they would make some way to secure those belongings in a place where it will not get stolen or damaged. A high level of home security fence would be more than enough to satisfy this need.
You can design your security fence in various ways. You must however, always keep in mind that the design your should choose would not sacrifice a degree in the safety of your properties. You should always consider the materials to be used in your desired design and the labor it would cost you.
Your security fence does not need to be installed as an independent security system in your home. High level security fences are just an added security to your home, which means any other security devices installed in your home could be connected to it. Part of the fencing solutions includes the construction of gates and hiring a fencekeeper.
Many supermarkets today are already selling high security devices because they are becoming so in-demand. Because of this, your options in security fencing designs are vast. The type of fence you choose will also determine how much security it could provide you. As much as possible, make your fences really high and install surveillance cameras in every corner. There are establishments, however, due to their importance, have to install high level security fences with barbed wires at the top.
There are also other numerous security devices today in which your security fences could complement. These modern devices are already known to add a high level of security to your home or property.
In rehabilitation facilities or precincts, it is required to add more security to fencing solutions by installing thick wire in the gates. There is an importance on which kind of wire you should install as part of your fencing solutions because the type of wire will determine how much security is needed for an establishment.
For households in the city, it is already necessary to install high quality gates are the home instead of the normal fencing solutions. There are modern gates already available today which can be unlocked and open wirelessly via a remote a control.
Privacy will also be another privilege that you could receive once you have installed high security fences. There are new designs that you could choose from today which could add how privacy to your life.
Overwhelmed by the Complexity of Homes? This May Help
Renovating Can Add Value to a Home
The desire to be able to have home improvements can actually be because of various reasons. You might have a random wish and this could be one reason behind this. Your wishes can as a matter of fact turn into reality and this is what you have to keep in mind. What you need to know about this is that this is actually a home improvement tip that you should keep in mind. Hiring a builder is what you need to have when you will avail of the home renovations.
The kind of builder that will be offering you a price per square foot that is at a very low price is what you call a baiter. The kind of price that will be offered to you will really be able to catch your attention. This will then make you decide to give a call to a custom builder. You will also now be able to realize that the price offered to you did not include every detail such as all permits and site work. And to make matters worse, the price that was given to you is for the materials that are sub standard or low grade materials.
In order for you to be able to see yourself the materials used and the build quality you should visit custom homes that are under construction. Asking if the workers like to work with the custom home builder is also a good idea. But as a reminder, make sure that you will not be taking up too much of their time. There is another aspect that you need to be able to take a look into and that is none other than the condition of the job site. Is it messy or sloppy?
Due to the inefficient fixtures or replace the broken fixtures is another reason why a home owner will have home renovations. There could be certain aspects in your home that are out dated which is in fact another reason for the rise of this need. There is actually another great home improvement tip that you should bear in mind and that is for you to simply have the color scheme changed. You can actually increase the value of your home through this manner.
There is a need to be able to do the necessary home improvements most especially if the home that you have is what you want to sell. Various ways can actually be done in order for you to attract a buyer and what you have just read is one of these methods.
Before you will start the project you need to make sure that you will be able to have your plans evaluated first. In order for you to make sure that you will not be able to make a mistake, you need to make sure of this.
6 Facts About Improvements Everyone Thinks Are True
Factors to Consider When Buying a Renovated House
Buying a house is an endeavor that comprises of a lot of money. Consequently, it is essential that you find the most appropriate house so that you cannot be disappointed. Since there are very many varied kinds of houses it is essential to know the factors that are important in searching for home.
Also, there are many elements that you are supposed to take into consideration. When you focus on just a single house, you might realize later that it is not the best option for you yet you will have spend a lot of time on it. Also, you can ask for help from different professionals such as a legal representative or a real estate agent. You might move into your new house and realize that there are some areas that need to be renovated and hence you should not use all of your money. Remember that different houses costs different prices and hence the need to know the one that matches your budget. Also, ensure that you take advantage of the fact that the Internet is very resourceful and hence it is easy to find a house.
The other essential factor when searching for a house is the location. Ask about the level of security in that particular area, availability of hospitals and other important facilities. Similarly, it is essential to consider if the house is filled with criminals or not.In case it is your first time then you should research as much as possible. In case you have a big family then you should look for a house that is spacious.
The work of a real estate agent is to help his customers to find a house and therefore you should work with one. Real estate agents are well informed regarding the different houses as well as their locations. Therefore, ensure that you search for a real estate agent that communicates effectively. Also, you should only pick a real estate agent that is able to explain all the details to you until you understand. The aspect of speed is very important in the real estate sector and therefore ensure that you hire a real estate agent that will be quick to inform you about a vacant house so that you can make a decision fast. Moreover, ensure that you arrange for a personal meeting so that you can ask them as many questions as possible before hiring them. Also, go through their websites and determine if the information is professionally arranged. Similarly, you should not select the first professional that you meet since there are others in the market that are more experienced and competent.
Suggested Post: description
A Simple Plan: Houses
Things to Look For When Opting For a Home Improvement Contractor
In most cases a person exactly gets what they pay for and this is never truer than in when planning to conduct a home remodeling project and a key part of this is selecting a home improvement contractor and going by price only as the only key determinant can be a huge mistake. With the proper planning and having a knowledgeable contractor the client can be sure of getting a great job done at a good price and also enjoying the process of home remodeling with the rest of the family.
The ability to connect with a contractor is a critical determinant since the person has to be sure that they can easily talk with the client and the client needs to make sure that they agree with the contractor regarding their goals. The customer has to make sure that the contractor has the required experience to handle the project and that they have handled the project in the past because various remodeling projects such as kitchen remodeling or bathroom remodeling have some technical aspects that need someone that has prior experience. It is vital to state that communication is also vital to look into because the person needs to communicate with the home improvement contractor regularly thus they need to be able to contact through phone, email or
text messages.
It is good to state that the client needs to comprehend that the price reflects the quality of the project that they will get and the customer needs to confirm some things such as recommendations on how the project should take place and if it is worth to cut corners in the end. The cheapest bid is not always the best and the person needs to request for a written note of the materials vital for the project and the clients should remember that a low bid might show that the contractor uses low-quality materials or is desperate for work and a more accurate bid is most likely to be somewhere in between.
The potential client has to know the credentials of the contractor because abbreviations before the name of the contractor usually represent certifications from national trade organizations that shows that the firm belongs to some organizations that hold them to a strict code of conduct. Some of those titles include terms like certified aging in place specialist (CAPS), certified graduate remodeler (CGR), National Association of Home Builders (NAHM) membership and the local Building Industry Association (BIA) membership. The customer has to have insurance both worker's compensation and liability insurance which will remove all liability from the client in case any accident happens while the contractor is working on the premises of the home of the customer.
Reference: website here


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Macadamian Selected by MED3OOO for Industry Changing Healthcare Product(February 29, 2012)
Ottawa (PRWEB) February 29, 2012
Macadamian a global leader in healthcare software product creation, today announced that it will be partnering with MED3OOO to develop a breakthrough product that will expand usability and adoption of technology in the ambulatory clinical setting.
The launch of this new product will come at an integral time, when physicians are tasked with meeting constantly changing regulations and reporting while simultaneously providing the highest level of care. This new product will address many of the challenges physicians now face.
We chose Macadamian because of their expertise in user experience design and software development in the healthcare sector, said Steve Ura, CTO of MED3OOO. This product will take our already existing robust solution offerings and put them far ahead of anything in the marketplace today.
We are honored to have been selected by MED3OOO to contribute our user experience design and agile development expertise to the evolution of the highly regarded MED3OOO suite of products and services" said Fred Boulanger, CEO of Macadamian.
For more information about Macadamians healthcare software practice, visit http://www.macadamian.com/industries/healthcare
About MED3OOO
MED3OOO is a leading provider of healthcare management and technology services that improve outcomes for providers, health plans, and the patients and employees they serve. The Company provides a broad array of proprietary solutions for physician groups, hospitals, health systems, health risk organizations, and state and local municipalities, enabling them to reach their maximum potential with respect to operational, financial, and clinical results. Through the integrated application of systems, operations, analytics and domain expertise, MED3OOO serves as the premier strategic operations partner for the healthcare community. The Companys depth of knowledge across its services, economies of scale, infrastructure, and ability to offer and manage disparate information systems provide MED3OOO with a distinct competitive advantage in the rapidly evolving healthcare industry. Each of the components of MED3OOOs product and services suite is a critical competency for moving toward the delivery of accountable care.
For more information visit http://www.MED3000.com or contact [email protected].
About Macadamian
Macadamian is a global leader in software product creation providing a complete range of product strategy, user experience design, and software engineering services to clients around the world, including healthcare industry leaders like MED3OOO, Cardinal Health, Elsevier, and Telus Health. Macadamian has a track record of helping clients create successful products on Android, iOS, Web 2.0 & RIA, Windows, and Mac OS X. Additional information is available on our website or by following Macadamian on Twitter and LinkedIn.
Media Inquiries
Didier Thizy, Director, Healthcare
613.739.5976 x136
Read the full story at http://www.prweb.com/releases/2012/2/prweb9234773.htm.
Page: 1
Related Keywords:computing and information technology, satellite technology, software, wireless technology, science and technology, technology (general), identification technology, agricultural research and technology, fishing industry, healthcare provider, cinema industry, radio industry, television industry, music industry, process industry, healthcare policy, computing and information technology, satellite technology, wireless technology, company information, science and technology, technology (general), identification technology, agricultural research and technology, economy, business and finance, waste management and pollution control, financial and business service, business enterprises,

subset: commoncrawl


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1. Pack Knife
Saturday, August 25, 2012
DIY Survival Gear - Sheath Mod for Pack Knife
1. Pack Knife
4 comments:
- Double Tapper said...
Great post. My bud was handling a knife in a sheath at a gun show. The blade had somehow cut through the sheath and sliced his hand open while he was looking at the sheath.
- August 25, 2012 at 7:56 PM
- riverwalker said...
To: Double Tapper
I like to keep one of these less expensive fixed blades in all my packs. The only problem is that after sharpening the blade good it goes right through those nylon sheaths.
I got poked a couple of times with this one but fixed that in a hurry.
Just need to be careful when handling any type of knife...they're designed to cut and will cut you as well if you aren't being careful.
- August 26, 2012 at 4:27 AM
Very cool. Good leather sheaths have a leather choil in between the two front and back of sheath so that sharp edge does not cut the threads. It seems that only high quality (and price) sheaths do that nowadays.
- August 26, 2012 at 10:14 AM
- riverwalker said...
To: anonymous 10:14
I try to keep a small fixed blade in each of my packs...which can be expensive. I generally try to find a less expensive alternative.
If I can do a simple modification, sharpen the blade or do a re-wrap to bring it up to more satisfactory level of performance...it works for me.
It also helps you to appreciate good quality gear when you can afford it.
Thanks anon.
- August 26, 2012 at 10:35 AM


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Smart Casual Wear to Get You From Day To Night
Imagine it is Thursday. You have a full day at the office but have plans later for that long awaited date you've been, not so secretly, excited for. You are in your wardrobe, desperately looking for the right outfit. You can't seem to find a matching attire, and you feel like your evening is spoilt already. Should you go for your finest dress, designer clothes, or play it safe with some smart casual wear?
Sounds familiar, right?
Truth be told, such is the struggle nearly all women, including myself, go through almost every day of our lives. Well, maybe not the date part, but the choosing what to wear. Being glamorous and fashionable can be hectic, especially if what you want to wear for one event doesn't transfer seamlessly to another one, and we all know there is no time to go home and change.
What's the solution? Invest in quality, timeless, classic pieces. No, I'm not talking about wearing your go-to black dress over and over again, but finding the right clothes that you can dress up and down, depending on your activity. Consider your style, body shape, the season, and your preferences, and get to shopping.
Classy clothing and fashion tips for women
The founders of VANEO, an online boutique store, set out to create a line of clothing that both empowered and flattered a woman on the move. Whether it is day or night, if you're in the office or out on the town, having the right pieces and knowing how to put them together makes getting ready a breeze.
Browse through these simple tips and master the art of choosing the right dresses, tops, blazers and trousers for every occasion. Tour VAENO's website for inspiration and wardrobe essentials for every occasion.
When you have the right clothes, and you know it, you'll radiate self-confidence and charisma.
Consider the following:
Highlight your features
We all have to wear clothes; this is not an option. What you can choose, though, if how you go about it. Don't be content to throw just anything on, take pride in your appearance. Take a quick thought to what your best feature is and set out on a mission to find clothes that highlight it.
If you can't decide on your best feature because there are too many to choose from, just remember to show off one or two at a time. A subtle touch of mystery is always welcomed.
Have a plan for each occasion
It doesn't matter if you're attending a black-tie event, a Valentine's Day celebration, or going to your friend's wedding, you're going to need to plan for formal wear at some point. Don't be caught shopping last minute, settling for just anything just because you need to find something. Take some time and find the right formal wear or evening wear beforehand.
With your go-to outfits, you'll have plenty of time to pamper yourself finding the right shoes or getting your hair done.
If you are buying a blazer, be smart
There's only one rule here; the blazer MUST fit your shoulders. Beyond that, use the cut, length, style and color to reflect your personal style.
Let your official wear work for you
Do you have a colleague who is always impeccably dressed? You know the one who always knows what to wear. Who blends in perfectly, but stand out just enough to draw attention?
No, it's not magic, you can pull this feat off too. Half the battle is finding pieces that fit your body correctly. Think V-neck sweaters to elongate your torso, appropriate length skirts that still allow you to move around, and always, ALWAYS invest in a pair or two of proper fitting trousers.
Keep all these points in mind, find the right clothes, and you'll have no problem dressing for any occasion. Just try to be modest, when you're the ones who's turning all the eyes.


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Lentils and Rice
Recipe by Sumisan
This is so simple but SO delicious! I first came across it in a marilu henner cookbook, but it is definitely a keeper!
Top Review by Marlene.
This recipe was a huge stretch for us , so I'm not going to leave any stars as I believe it was mostly a 'taste' issue with us. This was the first time I've ever tried brown rice or lentils. After about 40 minutes on a low simmer , there was no more liquid to soak up and it had started to stick to the pan. There was quite a bit of uncooked rice left in it. This is NOT a total washout for me though! Even though I might not have enjoyed the flavor so much of this as a side dish , I saved and froze the rest of it and am planning on making it an addition to a rich vegetable beef soup soon! I think they'll go great in that for us. Plus, simmering in the soup , the rice should finish up cooking too! :) Thanks for posting the recipe and thanks for getting me to broaden my horizons a little bit!!! :)
See Discussion:1 Review
Ingredients Nutrition
- 1 cup lentils
- 1 cup brown rice
- 4 cups water
- 1 onion
- 2 garlic cloves
- 2 tablespoons butter
- 1 bay leaf
- 1 teaspoon salt
- 1⁄4 teaspoon pepper
Directions See How It's Made
- Saute onions and garlic in butter pretty low so that garlic doesnt get bitter.
- Add water and the lentils and rice. Cover and cook for about 1 hour.
- It is good alone but adding more butter before eating makes it extra creamy!
- dont forget to remove the bay leaf and salt and pepper to taste (you dont have to go by the measurements on those!).


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Mr Meacher's hand is not the strongest. Once described as Tony Benn's representative on Earth, he belongs to a fast fading breed, the genteel left-winger. Moreover his new education colleagues may bear historical grudges. Higher education spokesman Bryan Davies, for example, whose Oldham Central seat is abolished at the next election, was worsted by Mr Meacher in the selection fight for the re-constituted seat of Oldham West and Royton just next door.
This is the second time the new Employment spokesman has fought off an internal challenge for Oldham West. When it was re-drawn in 1983 he beat a candidate called Charles Morris, the outgoing Openshaw MP. Who is, of course, the father of Estelle Morris, rising star of Labour's education team.
Still no luck for Eric Forth in his search for a safe Conservative seat. Rejected by Mid-Worcester, he now finds that the selection panel in Maidenhead has no use for a Minister of State at the DFEE. Nor, by the way, for Sir Paul Beresford, formerly leader of Wandsworth Council.
Elizabeth Cotterill, political adviser to Gillian Shephard, fared a little better, before falling at the last in the race for Altrincham and Sale.
Glad to say, however, that the right-wing former education minister Michael Fallon is still in the hunt, and has made it to the semi-finals of Kensington and Chelsea along with top motorist Nicholas Scott.
Great excitement for Andrew Turner, another Tory hopeful and director of the Grant Maintained Schools Foundation - the publicly-funded outfit which provides informationpublicity to would-be opt out schools.
Mr Turner has been lucky in love and is now engaged to Carol Dennett of Clifton Reed Consultants - a firm which sells computer systems to people including, as it happens, GM heads. Mr Turner has been less lucky in his search for a safe Conservative seat, although news of his imminent state of grace may give him the edge he needs.
When are the nuptials? "It will have to be after the local government elections," he romantically replied.
When you've been chief executive of Brent for six years you get used to living from day to day," Michael Bichard told the Employment Select Committee. Mr Bichard has just seen off his rival, the whistle-blowing Sir Tim Lankester (of Pergau fame), in the fight to be sole permanent secretary in the merged DFEE.
Tough going perhaps. But the wilds of local government have their own horrors.
It was during his time as chief executive of Brent Council in London, for example, that Jasmine Beckford died a violent death at the hands of her stepfather. The subsequent report was heavily critical of the borough's social services and led to the child protection legislation in the Children Act.
He then moved to take up the top job in rural Gloucestershire, where all now wait for the inevitable inquiry into whether the police and the social services could have done more to prevent the many deaths at the centre of the West trial.
The comfy old DFEE looks quite a good bet.
The Department for Education and Employment has got a new logo: DfEE with the "D" in a little maroon square and the f in italics. This piece of champion design was a snip at Pounds 15,000 which, according to the department, covered the cost of something called development as well as the emblem itself, drawn up by the Central Office of Information. This year's DFEE's publicity budget is Pounds 5.53 million.
Warwick University is cruising the academic highways, eager to lure top names to its new Institute of Education.
Among the latest soccer-style signings are Geoff Lindsay, vice-president of the British Psychological Society, transferred from Sheffield Council to a new professorial post on the windswept campus.
He is joined by Professor Robin Alexander, best known for the Leeds and "Three wise men" reports on primary teaching. Chris Husbands of the Historical Association will leave the University of East Anglia for a readership. A professor and a reader are still wanted, but tight-lipped supremo Professor John Tomlinson is keeping mum.
Top of Education Secretary Gillian Shephard's Xmas shopping list must be The Book of Virtues: a treasury of great moral stories. This is a terrifying tome edited by William J Bennett, a former Secretary of Education in the Reagan Administration, which carries an endorsement from Gillian.
"I trust this book will provide (children) with a fund of enriching tales, " writes Mrs Shephard.
She is surely also thinking of her Cabinet colleagues. Among the entries - divided into chapters with headings such as Compassion, Self-Discipline and Honesty - are the following gems: "Undertake not what you cannot perform, but be careful to keep your promise" (George Washington); "Train for ill and not for good" (AE Housman); "The man who misses all the funIs he who says, 'It can't be done'" (Anon). One they have taken to heart.


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What is JotForm?
JotForm is a free online form builder which helps you create online forms without writing a single line of code. No sign-up required.
At JotForm, we want to make sure that you're getting the online form builder help that you need. Our friendly customer support team is available 24/7.
We believe that if one user has a question, there could be more users who may have the same question. This is why many of our support forum threads are public and available to be searched and viewed. If you'd like help immediately, feel free to search for a similar question, or submit your question or concern.
Form fields need to be tapped twice in iOs devicesAsked by dyrck on January 19, 2016 at 08:36 AM
Hi I have a problem with a form when viewed on iOs devices. The form fields need to be tapped twice before they accept text and the keyboard appears. I have made only one previous form and this wasn't a problem. Any suggestions?
JotForm Support
I cannot replicate this problem in your form. I think the issue is related to the formsite form in the page that overlaps the jotform form. You may consider removing that form. If removing doesn't help, please try re-embedding the form using our iframe method: http://www.jotform.com/help/148-Getting-the-Form-iFrame-Code.
Thanks Welvin,
I have cured the problem by turning off hover text. It would seem the first tap was being interpreted as a mouse hover. You may have accessed the test site after I made that change.
Thanks for caring.
JotForm Support
That's great to know. Please contact us again if there are any problems.


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Hey there, time traveller!
This article was published 10/12/2010 (2446 days ago), so information in it may no longer be current.
In many ways technology has made the world smaller, but when it comes to workplace communications, it seems we've never been further apart.
Don't get me wrong; there is plenty good about the speed and volume by which we can communicate via email, voice mail and instant messaging at work. Other than the fact that digital information can be open to interpretation, redirected and therefore, misleading. Not to mention that sending out one message to several recipients tends to delay decision making and makes it easy for the group to pass the buck and avoid consensus or commitment.
While technology does have its place at work, the main problem with it is that it is increasingly pushing face-to-face interaction by the wayside. One global survey revealed that 67 per cent of managers said their organization would be more productive if their superiors communicated in person more often. It seems entirely possible that in today's click-and-send digital world, we're actually yearning for more human contact.
Often, we rush to get things done by email or text message when it would be more effective to simply pick up the phone or talk things over in person. As a result, we are missing out on the many benefits of face-to-face communication.
Quite often, how we say something is as powerful as what we say. So the next time you prepare to send out a digital memo or directive, consider that tone, inflection and body language account for 93 per cent of the messages our brains interpret, while words make up a lowly seven per cent.
Face-to-face interaction leads to better organizational understanding, strengthens trust and builds high-performance teams. But that's not all:
1. Face to face meetings occur in real time, while computer-generated messaging is often delayed because the messages are not read right away or are intercepted by a technical glitch.
2. Face-to-face meetings allow participants to accurately observe both verbal and non-verbal communications of others. Subtle but important nuances such as voice inflections, hand gestures and facial expressions just don't come across in an email message.
3. Face-to-face meetings are an opportunity to build strong social relationships and create social bonding that in turn fosters a sense of belonging. Such gatherings help people to identify with the organization and see how they fit in, which instils pride and loyalty.
4. Face-to-face meetings ensure that detailed information can be disseminated, facts can be checked, issues can be identified and addressed, input can be collected and questions can be asked -- all at once.
5. Face-to-face meetings teach the ins and outs of the organization and its culture. By observing others, individuals learn how things work, how others behave and idiosyncratic rules such as the importance of showing up on time for scheduled meetings.
6. Face-to-face meetings give participants a window to silently evaluate the competencies of the people they work with. For example, spending time with a leader with admirable verbal presentation skills may inspire an employee to improve their own public speaking abilities.
7. Face-to-face meetings can veer from their primary purpose and make way for valuable side discussions that can help to complete tasks, share ideas and inform others about the status of ongoing projects. Getting sidetracked is not always a bad thing.
8. Face-to-face meetings are conducive to a fun working environment because they allow participants the freedom to inject humour and express emotion that is absent from digital communications.
9. Face-to-face meetings keep good managers in touch with their people. It allows them to recognize good work and give pats on the back, hear the latest from the worker grapevine (and nip rumours in the bud, if necessary) as well as gauge employee morale.
10. Face-to-face meetings can alleviate the feelings of isolation and stress that come from sitting alone at a desk all day. Humans are social creatures by nature. By interacting in person, people can obtain and offer social support through sharing ideas, assistance, news and information with one another.
When employees interact in person, they naturally feel more engaged with one another, with their work and with their organization. That's something that simply can't be communicated with instant messaging.
-- With reporting by Barbara Chabai
John McFerran, PhD, F.CHRP, is managing director of Boyden Global Executive Search. He can be contacted at firstname.lastname@example.com.


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Are online estate agents any good?
Which is regarded as the best online estate agent with the best internet coverage?
Asked on Mar 24 2011, Selling in Otley | Report content
Answers (17)
Sort by: Oldest | Recent | Highest rated
They can be but like a traditional agent, you should spend a little time to look around and find the right one.Answered on Mar 25 2011, Report content
You'd be mad to use an online agent. A good local agent can not only promote your area but will have loads of buyers attracted by other stock in the area to whom he/she can show your property. Most people do not buy the property about which they enquired! So any sole reliance on a direct internet sale is about as likely as peace in the middle east. And with agency fees in the UK being the lowest in the world by a long chalk, what would be the point of some perceived saving in any event. Definitely get what you pay for here!! Good luck.Answered on Mar 25 2011, Report content
Sorry, I have to disagree. From experience (High Street estate agent for 5 years and sourcing agent for 10 years) you can find as good if not a better service online, dependent on the agents. An online agent provides nationwide access to your property, opening up a larger market. Fees are always negotiable online or other so again it comes to each individual.Answered on Mar 25 2011, Report content
All local agents are online anyway and any who claim that an online agency expands the marketing is missing the point. eg it could be claimed that by being on the web at all the property is within reach of billions of people. So what? Only those specifically looking for my type of property in my area are of any interest. Then I need a good agent to swing people onto my property who might otherwise not have viewed.Answered on Mar 25 2011, Report content
I think a local presence is key to getting a quick turn around when it comes to selling/letting a property. During pre-launch we were marketing some properties for a new landlord, however, we did not have an office open in the area so relied completely on Rightmove. We lost out on both of these properties to competitors because they had a local presence and had people walking in to their shop making enquiries. We keep a very close eye on our enquiry sources, and it is quite clear that without the office presence and people walking in to speak with us, we would most likely not have been successful in providing our clients with a quick let to quality applicants. I appreciate that you are asking about sales but I feel that this applies to both sales and lettings. Also, local market knowledge is key when trying to sell or let properties in this difficult market.Answered on Mar 25 2011, Report content
Like traditional estate agents, some are good and some are not so good. It depends on what it is you want and how much of your own time you want to spend letting or selling your property. One thing online agents do not normally do is viewings, however some do so make sure you understand what is on offer for what you pay. Generally using an online agent will mean a large saving because online agents do not normally have a shop window. I think it is well known that the vast majority of those looking for property search on internet property portals.Answered on Mar 25 2011, Report content
Actually 'All' local agents are not online, I know of several in my home town who do not have a presence online. So essentially you are saying that people in town A would not look for a property in town B? Are you an estate agent?Answered on Mar 25 2011, Report content
I'm a tech adict, but chose to have a retail outlet too. Why? Ask yourself what proportion of costs rent and rates are of a proper estate agent? Our rent and rates are equivalent to the value of 2 Fully managed lets a year! what other costs do online agents save? BTW we've had 3 clients walk in this year already. The internet is great but cost/benefit analysis says (to me) retail presence works for good agents in good locations.Answered on Mar 25 2011, Report content
You could give us a go, we list on all of the top property portals and have a good track record of selling homes quicklyAnswered on Mar 28 2011, Report content
I don't see why an online estate agent can't be every bit as good as a high street estate agent. Why not try selling or renting privately? There are free sites you can use to create your own website and many free sites where you can advertise property, you would save even more then!Answered on Apr 7 2011, Report content
We offer the best of both worlds. We are an online agent based in Leeds and deal with the whole Leeds area and would be delighted to sell your property. We have sold property as far out as Huddersfield, offering strong advertising on websites as well as running a local mailing list. I take on board rrawling's comments about operating a patch, which is why at present we offer a local online estate agency service with a personal service you'd get from your high street agent.Answered on Jul 26 2011, Report content
I found this site very useful: www.compareonlineagents.com as it helped me to look for the right online agent based on my needs. Totally recommend it.
Web reference: http://www.compareonlineagents.comAnswered on Feb 6 2014, Report content
A good professional or company regardless is worth hanging onto. It doesn't really matter if they are High street or Online. What does matter is being able to measure what service best suits you when you sell your house. Naturally, the cost will figure into that. The problem I have with most high street agents is that most don't actually sell your house in the first few weeks. This is their prime time to sell and your best chance to get buyers. It's then common for the Agent to ask you to drop your price, and most of us do! The financial drop of let's say £5-10K is a lot, but for the Agent it's peanuts. Remember they are taking a percentage of your selling price, so it's actually easy for them to ask you to drop to make a quick sale. Once the 2 week period is over, the Agent moves onto their next client. As I haven't found any high street agents worth holding-on to, I've used these guys in the past, and they use established Agents who are motivated and have a good track record. The site is free and dead quick to use. You will be amazed how cheap they are without cutting corners. www.compareonlineagents.com
Web reference: http://High street Agents or Online?Answered on Feb 22 2014, Report content
Most online estate agents have similar internet coverage nowadays simply because Zoopla have merged with many of the smaller portals. There is a mis-conception that online estate agents do not offer a personal service, this is actually incorrect. Online estate agents are office based so have a lot more time to speak to clients and solve any problems that occur. Try getting hold of a high street negotiator, they are out of the office most of the day!
Web reference: http://www.turtlehomes.co.uk/sell-property-online/propert...Answered on Oct 7 2014, Report content
Hi -Saw this thread whilst trying to do my own evaluation of online estate agents versus traditional high street. I invited 2x traditional EA to evaluate my flat and outline their services. I couldnt see ANY TANGIBLE reason why they wanted £2000 more than the online companies! In the end we used House Network (as recommended on mumsnet, thanks to everyone there) - they were brilliant!! Everything went really smoothly and after using House Network I can definitely say that theses guys only cared about giving good customer service - that meant being available and accurate, timely information to all parties concerned and no exaggeration or playing one offer against the other. Unfortunately I cant say the same about EITHER of the EA representing the 2 homes we were interested in buying. Both were much harder to contact (early finish, no sundays, long hold times) and one of the EA was definitely exaggerating offers as the other buyers were friends of friends - caught red handed! If anyone is trying to make the same decision we were 4 months ago I can whole-heartedly recommend them. We paid £800 for photos (they were better than both the traditional EA we tried first!), floorplan, EPC, marketing on rightmove etc, viewing arrangements and facilitated the offers stage - you can use this code for a 5% discount at HN :-) HQJKCZRIDAAnswered on Jun 10 2015, Report content
I have nothing but praise for HouseNetwork. They do everything right. Pictures/Listing/keeping you up to date. They chase all viewers for feedback, they are all the good things an estate agent should be. It may not be for everyone - you have to do your own viewings which we didnt have a problem with but can understand if some people do. They won't drag unwilling viewers around like high street agents to make it look like you are getting interest. When looking to buy in the past high street agents have taken me to loads of places knowing it isnt suitable. I have never been able to figure out why paying 1 - 2% of the value of your property to an high street agent was ever a good idea - they never earn it! I got full asking price - if your worried about the online agent not knowing the value of your property then get a high street agent to value it beforehand. They will give you in most cases a high value to try and get you to sign up. In my case the high street agent undervalued - its not there fault - its a matter of what people are willing to pay. You will get less viewings with an online agent but they will be viewings from people genuinlly interested. No one gets put off from a property becasue of the estate agent. One critism I do have of house network is there sunday service - they must outsource there call centre on a sunday and probably late at night as they are 24/7. The outsource company arent really any good unless its a straightforward query.Answered on Dec 18 2015, Report content
I've sold my property and my dad's property through a new-looking company doorstepagents.com They're pretty good. I paid £99 for one and £199 for the other. Both properties were in London, one in Harrow, one in Finchley... so all in all, I saved about 14k worth of fees (expensive houses). They had a lovely agent come round, and they followed their branding of "old fashioned agents really fashionable price" - as he was cool, smart and valued it same as high street. I had with high street for 6 months, tied in, nothing. Here I wasn't tied in and sold in Sept within 1-2 months... and from what I've seen, they were the CHEAPEST agency of them all and top 10 on trustpilot (that's where I found them).... Loved it.
Web reference: http://Doorstepagents.comAnswered on Feb 11 2017, Report content
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The Raven
Tempter (note the capital T) (86)
balm in Gilead (Gil-ee-ad) (89)
A perfume mentioned in the bible named after its place of origin
Aidenn (Aid-en) (93)
Another spelling for eden referencing the garden of eden
desolate (87)
A place deserted of people and bleak/empty, or to make something bleak/empty
undaunted (87)
Not discouraged or disheartened
laden (93)
Heavily loaded or weighted down
sainted (94)
being formally recognized as a saint
fiend (97)
An evil spirit; a demon.
plume - definition having to do with birds (99)
a long, soft feather or arrangement of feathers used by a bird for display or worn by a person for ornament.
pallid (104)
someone being pale, usually because of sickness


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The Magic Hour(2016)
A novel by Crystal Allen
This is the second installment of my personal journey, the first being Like Water. Join me as I make my journey on this trip we call life. Some of us "get it" early in life, and some of us have to learn the hard way. I've taken the latter. However, in The Magic Hour, I've begun to wake up and see that I have been engaging in some magical thinking by assuming that life is going to just drop my dreams into my lap, hoping against hope that my prayers will bring a change to my mother and my life when in reality, the person who needs to change is me. I am to learn this by living through harrowing hidden experiences with my family. Pushed to the limit, what decisions will I make? How will I turn things around? The lessons that I've learned as a child, which I thought were a bit archaic and cruel, will serve me well.
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May 2016 : USA Paperback
|Title: The Magic Hour
Author(s): Crystal Allen
ISBN: 1-68348-374-X / 978-1-68348-374-8 (USA edition)
Publisher: Page Publishing, Inc.
Availability: Amazon Amazon UK Amazon CA
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September 2016 : USA, Canada, UK Kindle edition
|Title: The Magic Hour
Author(s): Crystal Allen
Publisher: Page Publishing Inc
Availability: Amazon Amazon UK Amazon CA
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I payed the toll for the person behind me 🙂
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Tasigna® (Nilotinib) is a recently approved BCR-ABL kinase inhibitor by the Food and Drug Administration, which is indicated for the treatment of drug-resistant chronic myelogenous leukemia (CML). The efflux of tyrosine kinase inhibitors by ATP-binding cassette (ABC) drug transporters, which actively pump these drugs out of cells utilizing ATP as an energy source, has been linked to the development of drug resistance in CML patients. We report here synthesis and characterization of a fluorescent derivative of Tasigna to study its interaction with two major ABC transporters, P-glycoprotein (Pgp) and ABCG2, in in vitro and ex vivo assays. A fluorescent derivative of Tasigna, BODIPY® FL Tasigna, inhibited the BCR-ABL kinase activity in K562 cells and was also effluxed by Pgp- and ABCG2-expressing cells in both cultured cells and rat brain capillaries expressing Pgp and ABCG2. In addition, [3H]-Tasigna was also found to be transported by Pgp-expressing polarized LLC-PK1 cells in a transepithelial transport assay. Consistent with these results, both Tasigna and BODIPY® FL Tasigna were less effective at inhibiting the phosphorylation of Crkl (a substrate of BCR-ABL kinase) in Pgp- and ABCG2-expressing K562 cells due to their reduced intracellular concentration. Taken together, these data provide evidence that BODIPY® FL Tasigna is transported by Pgp and ABCG2, and Tasigna is transported by Pgp. Further, we propose that BODIPY® FL Tasigna can potentially be used as a probe to study Tasigna in imaging Pgp- and/or ABCG2- expressing cancer cells and other preclinical studies.
Chronic myelogenous leukemia (CML) and Philadelphia (Ph)-positive acute lymphocytic leukemia (ALL) are caused by the unregulated activity of chimeric Bcr-Abl protein in white blood cells 1. Gleevec® (Imatinib mesylate) is a first generation BCR-ABL kinase inhibitor that competitively inhibits binding of ATP to the kinase and inhibits the phosphorylation of cellular targets 2. Treatment of CML patients with Gleevec was shown to be highly effective in clinical studies 3-5. However, several patients showed resistance to Gleevec or experienced a relapse after initial success with the drug 6, 7. Approximately 50% of those patients carry resistance-associated point mutations in the ATP-binding pocket of BCR-ABL 2, 8, 9. In the remaining 50% of Gleevec-resistant patients, several mechanisms of resistance have been described, including amplification or mutation of the BCR-ABL gene and active efflux of drug from the resistant cells by ATP-binding cassette (ABC) drug transporters 10-13.
Tasigna® (nilotinib, AMN107; marketed by Novartis) is a new, orally active tyrosine kinase inhibitor (TKI) with a higher binding affinityand selectivity for BCR-ABL kinase than Gleevec 14. Tasigna is 20 to 50 times more potent than Gleevec in Gleevec-sensitive CML cell lines and 3 to 7 times more effective in Gleevec-resistant cell lines 14.
TKIs, including Gleevec and Tasigna, have recently been found to modulate drug resistance mediated by ABC drug transporters in in vitro and in vivo studies 15-17. Although these TKIs were developed to interact specifically at the ATP-binding sites of the kinases, we showed earlier that Gleevec interacts with both Pgp and ABCG2 at the transport-substrate site(s) and not at the ATP-binding site(s) of ABC drug transporters 18. Existing literature does not provide definitive data on the effectiveness of TKIs (specifically Tasigna, which is used to treat imatinib-resistant CML patients) in ABC-drug-transporter-expressing CML cells 18. Therefore, we sought to address this aspect of TKI-ABC drug transporter interactions using a fluorescent and a radiolabeled derivative of this drug. We synthesized a fluorescent (BODIPY® FL ) derivative of Tasigna and this study highlights the interaction of this fluorescent derivative (BODIPY® FL Tasigna) with Pgp and ABCG2 using both cell-based in vitro and ex vivo assays. In addition, we studied the transport of a radiolabeled [3H] derivative of Tasigna in polarized LLC-PK cells expressing Pgp. The results from these two derivatives of Tasigna demonstrate that Tasigna is transported by Pgp and ABCG2. These data may have important pharmacological and toxicological significance, as Tasigna is an orally active drug recently approved by the FDA for the treatment of CML and its safety and efficacy profile are still under investigation.
Mitoxantrone, MTT dye, rhodamine 123 and all other chemicals were purchased from Sigma (St. Louis, MO). [125I]-iodoarylazidoprazosin (IAAP) (2200 Ci/mmole) was from Perkin Elmer Life Sciences (Wellesley, MA). XR9576 and PSC833 were a kind gift from Xenova (UK) and Novartis (Basel, Switzerland), respectively. FTC was synthesized by Thomas McCloud, National Cancer Institute, NIH. The BODIPY® FL labeling kit and BODIPY® FL prazosin were purchased from Invitrogen Corp. (Carlsbad, CA), and [N-ε (4-nitrobenzofurazan-7-yl)-D-Lys8]-cyclosporine A (NBD-CSA) was synthesized by R. Wenger (Basel, Switzerland) 19. [3H]-Tasigna (370-740 GBq/mmol) was custom prepared by using the [3H] exchange method by American Radiolabeled Chemicals, Inc. (St. Louis, MO).
pCDNA3.1-HEK, Pgp-HEK, ABCG2-HEK and K562-ABCG2 cells were kind gifts from Dr. Susan Bates (NCI, NIH) and were maintained in DMEM (with 2 mM L-glutamine and 10% FBS) with 2 mg/ml G-418. K562 and K562/i-S9 (Pgp) cells were provided by Dr. Eugene Mechetner (Oncotech Inc, Tustin, CA). K562, K562/i-S9 and K562-ABCG2 were maintained in RPMI media (with 2 mM L-glutamine and 10% FBS) 20. LLC-PK1 control (ATCC, Manassas, VA) and LLC-PK1-MDR1 cells were grown in medium 199 (3% (v/v) FBS, 1% Penicillin/Streptomycin and 500μg/ml Geneticin). The expression levels of Pgp and ABCG2 in HEK and K562 cells were different, as demonstrated earlier 20-23.
LLC-PK1 cells expressing human Pgp were generated by transfecting these cells with pcDNA3.1 plasmid containing human wild-type Pgp cDNA using Lipofectamine 2000 (Invitrogen, CA). After transfection, stable recombinant cells were isolated and the expression recombinant human Pgp on the cell membrane were verified by western blot analysis and Flow cytometry using Pgp specific monoclonal C219 and MRK16 antibodies, respectively and Calcein-AM accumulation assays.
Male Sprague-Dawley rats (10 weeks old, 300 g average body weight) were purchased from Charles River (Portage, MI). All animal protocols were approved by the Institutional Animal Care and Use Committee of the University of Minnesota (IACUC protocol # 0710A17842; PI: Björn Bauer) and were in accordance with AAALAC regulations and the Guides to Animal Use of the University of Minnesota and NIH animal use guidelines.
Crude membranes from High-five insect cells expressing Pgp were prepared as described elsewhere 24. The protein content was estimated using the amido black B-dye binding assay, as described previously 25.
Accumulation assays with BODIPY® FL Tasigna (0.5 μM) were performed as described previously 26. For all samples, 10,000 events were counted and the analysis was performed with Cell Quest software (Becton-Dickinson Immunocytometry systems). The mean fluorescence intensity was calculated using the histogram stat program in Cell Quest software.
pcDNA3.1-HEK, Pgp-HEK and ABCG2-HEK cells were grown on 12-well glass bottom chamber slides for 14-16 hr (Nalge Nunc International Corp, Naperville, IL). These cells were incubated with 0.5 μM BODIPY® FL Tasigna (in IMDM media containing 5% FBS) at 37°C for 45 min. The cells were washed twice with cold PBS and images were acquired using an oil immersion objective (100 X) in a confocal microscope (MRC-1024, Bio-Rad, Hercules, CA, USA).
For ATPase assays, crude membrane protein (100 μg protein/ml) from High-five cells expressing Pgp and ABCG2 was incubated at 37°C with varying concentrations of Tasigna and ATP in the presence and absence of 0.3 mM sodium orthovanadate and the vanadate-sensitive ATPase activity was determined by estimating the amount of inorganic phosphate released, as described previously 24.
Photoaffinity assays were performed by incubating crude membranes (1 mg protein/ml) from Pgp-expressing or ABCG2-expressing High-five cells with 0-20 μM of Tasigna for 10 min at 21-23°C in 50 mM Tris-HCl, pH 7.5 followed by addition of 3-6 nM [125I]-IAAP (2200 Ci/mmole). The samples were crosslinked and incorporation of [125I]-IAAP was determined as described previously 27.
Rat brain capillaries are known to express Pgp and ABCG2 28, 29, therefore freshly isolated capillaries from rat brains were used to monitor Pgp and ABCG2 transport function with fluorescent substrates including Bodipy-Tasigna® as previously described 30, 31. Brain capillaries were incubated for 1 h at room temperature with either 2 μM NBD-CSA, 2 μM BODIPY® FL prazosin, or 2 μM BODIPY® FL Tasigna. For each treatment, images of 10 capillaries were acquired by confocal microscopy (Nikon C1 laser scanning confocal microscope unit mounted on a Nikon TE2000 inverted microscope, 40x oil immersion objective, numerical aperture × 1.3, 488 nm line of a Spectra Physics krypton-argon laser (model 163C) in conjunction with a 515/30nm band pass filter; Nikon Instruments Inc., Melville, NY, USA). Confocal images were analyzed by measuring the lumenal fluorescence intensity of the above compounds as described previously 30, 31.
106 cells from LLC-PK1 (parental) and LLC-PK1-MDR1 (P-gp positive) cell lines were solubilized in protein extraction buffer (10mM Tris-HCl, pH8.0, 0.1% Triton X-100 (v/v), 10 mM MgSO4, 2 mM CaCl2 supplemented with 1% (v/v) aprotinin, 1 mM AEBSF, 2 mM DTT and 20 μg/ml micrococcal nuclease. Samples were lysed by freeze thaw following sonication in a bath sonicator. Equal amount of protein samples were separated by SDS-PAGE on 3-8% Tris-Acetate gel and transfer onto nitrocellulose membrane. The blot was blocked with 20% non-fat dry milk followed by overnight incubation with Pgp-specific C219 antibody (1:2000). Horseradish peroxidase-conjugated anti-mouse IgG was used as secondary antibody. The presence of Pgp was visualized by enhanced chemiluminescence reagents (Perkin-Elmer) according to manufacturer's protocol.
LLC-PK1-MDR1 cells were seeded at a density of 2 × 106 cells/24mm well on transwell costar polycarbonate filters (0.4μm pore size, Costar, Lowell, MA). Cells were cultured for 5 days with media changed once in two days. To confirm the quality of the cell monolayers, transepithelial electrical resistance (TEER) was measured with an epithelial voltmeter (World Precision Instruments, Sarasota, FL). Cell monolayers with TEER values above 200Ω were used for assay. The transport across the cell monolayer was conducted by adding [3H]-Tasigna (64 nM, 1 μCi/ml) to either the apical or basolateral side of the monolayer in the absence or presence of cyclosporine A (10 μM) or tariquidar (1 μM). Aliquots of medium (50 μl) were taken from the opposite side of the cell monolayer at 60, 120, 180 and 240 minutes, mixed with scintillation cocktail (10 ml) (Bio-Safe II) and the disintegrations per minute were measured using a Beckman Coulter LS-6500 liquid scintillation analyzer. The efflux ratio (B→A/A→B), in folds, were calculated by dividing drug efflux rate of (B→A) from (A→B) to evaluate Pgp-mediated directional efflux.
K562, K562/i-S9 and K562 ABCG2 cells were treated with 0.05-1 μM Tasigna or 10-20 μM BODIPY® FL Tasigna for 4 hr. BCR-ABL kinase activity was measured in total cell lysates by detecting the levels of P-Crkl, a BCR-ABL kinase target using P-Crkl (Tyr207) or total Crkl levels using CrkL antibodies (Cell Signaling Technology, Danvers, MA) according to the manufacturer's suggested protocol.
The synthesis of Tasigna was accomplished using a series of published methods 32. The complete synthetic scheme for BODIPY® FL Tasigna is shown in Figure 3. Detailed characterization of the intermediates in the synthesis protocol and an analytical trace demonstrating the purity of BODIPY® FL Tasigna is given in the supplementary information section.
Data are presented as mean ± SEM. A two-tailed unpaired Student's t test was used to evaluate differences between controls and treated groups; differences were considered to be statistically significant when P < 0.05. Sigmoidal dose-response curves and IC50 values were calculated using GraphPad Prism Software Version 4.01 (GraphPad Software, Inc., La Jolla, CA, USA).
To investigate the interaction of Tasigna with Pgp, its effect on the Pgp-mediated efflux of calcein-AM was determined. Control pcDNA3.1-HEK and Pgp-expressing Pgp-HEK cells were incubated with 0.25 μM calcein-AM in the presence or absence of indicated concentrations of Tasigna or 2 μM, Tariquidar (XR9576; a Pgp-specific inhibitor) at 37°C for 10 min. The total cellular fluorescence was monitored using flow cytometry as described in the Experimental section. As shown in Figure 1a, 1-2 μM Tasigna inhibited the efflux of calcein-AM in Pgp-HEK cells, while it had no effect on the accumulation of this compound in control pCDNA3.1-HEK cells. The inhibition of calcein-AM efflux by Tasigna was comparable to 2 μM XR9576, suggesting that Tasigna was a potent inhibitor of the function of Pgp.
To understand the mechanism of interaction of Tasigna with Pgp, we determined the effect of Tasigna on Pgp ATPase activity and its ability to displace IAAP binding in photoaffinity labeling assays. Tasigna inhibited the photolabeling of Pgp with [125I]-IAAP in a concentration-dependent manner with an IC50 value of 0.18 μM and stimulated ATP hydrolysis at very low concentrations, with only 0.19 μM required for 50% stimulation (Figure 1b and c). These results demonstrate that Tasigna interacts with the drug substrate binding site(s) on Pgp in a way similar to its interaction with drug substrate binding sites on ABCG2 reported earlier 33. Tasigna also stimulated the ABCG2-ATPase activity in a concentration-dependent manner [see Figure 3 in reference 33].
An important physiological function of Pgp and ABCG2 is to provide a pharmacological barrier for tissues present in the blood-tissue interphase such as in the blood-brain barrier. Since Tasigna inhibits the transport function of Pgp in cultured cells (Figure 1a), we then sought to determine if it was also effective in an ex vivo system consisting of freshly isolated, intact rat brain capillaries, which express both Pgp and ABCG2 and are an established ex vivo model to study blood-brain barrier function 34-37. Isolated brain capillaries were exposed to either 2 μM NBD-CSA (fluorescent Pgp substrate), or 2 μM BODIPY® FL prazosin (fluorescent ABCG2 substrate) for 1 h with or without Tasigna. In capillaries treated with Tasigna, lumenal fluorescence of both NBD-CSA and BODIPY® FL prazosin was reduced in a dose-dependent manner (Figure 1d and 1e middle panels). PSC833, a Pgp-specific inhibitor, and fumitremorgin C (FTC), an ABCG2-specific inhibitor, also reduced lumenal fluorescence of NBD-CSA and BODIPY® FL prazosin, respectively (Figures 1d and 1e, right panel). Quantification of steady-state lumenal fluorescence accumulation showed that Tasigna, PSC833, and FTC maximally reduced lumenal fluorescence to approximately 50% of control capillaries (Figure 1f and 1g). Note that the fluorescence remaining after inhibition of transport reflects passive diffusion and nonspecific binding of the dye to the tissue 36, 37. The IC50 concentrations for Tasigna to inhibit efflux activity were 3.46 μM for Pgp and 93.2 nM for ABCG2, respectively.
The effect of Tasigna on the cytotoxicity of other anticancer drugs is further demonstrated by the reversal of cytotoxicity assays where a non-toxic concentration of Tasigna in combination with the Pgp substrate doxorubicin was able to inhibit drug resistance mediated by Pgp in MDR1-transfected HEK cells (Table 1).
Since Tasigna targets the BCR-ABL kinase in CML cells, we evaluated its ability to inhibit BCR-ABL kinase activity in CML cells that overexpress Pgp and ABCG2. The BCR-ABL kinase activity was measured by monitoring the phosphorylation of Crkl (P-Crkl), a target of BCR-ABL kinase in K562 cells (a CML cell line) since this kinase is specifically expressed in this these cells. Tasigna was less effective at inhibiting the phosphorylation of Crkl in Pgp-expressing K562/i-S9 cells (Figure 2a, upper panel), and ABCG2-expressing K562-ABCG2 cells (Figure 2b, upper panel) compared to that in parental, control K562 cells. The level of total Crkl remained unchanged in these cells by treatment with Tasigna (Figure 2a and 2b, lower panels). The level of P-Crkl expression was quantitated by densitometric analysis. The IC50 value of Tasigna for inhibition of Crkl phosphorylation in K562 cells was 69.85 nM, while it was 329 nM for K562/i-S9 (Pgp) cells and 370 nM for K562-ABCG2 cells (Figure 2b). Tasigna was thus 4-to 5-fold less effective at inhibiting BCR-ABL kinase activity in Pgp- and ABCG2-expressing K562 cells compared to control K562 cells. A plausible reason for the reduced efficacy of Tasigna in Pgp- and ABCG2-expressing cells could be lower intracellular levels of the drug due to Pgp- and ABCG2-mediated active efflux from these cells as compared to control K562 cells.
The above described results indicated that active efflux of Tasigna by Pgp and ABCG2 in CML cells can lead to its reduced efficacy. However, there was no clear evidence that Tasigna was transported by Pgp or ABCG2. In order to address this question, we synthesized a fluorescent derivative of Tasigna (Figure 3) as described in the Experimental section and evaluated it in fluorescence-based in vitro and ex vivo assays. Previously, BODIPY conjugates of anticancer agents including vinblastine, verapamil and paclitaxel have been used as tools to determine transport function of ABC drug transporters 38, 39. The basic physicochemical properties of Tasigna and a truncated version of Bodipy-Tasigna molecule (the programs used can't deal with the multivalency of the boron in the Bodipy fluorophore so it had to be removed) are significantly similar (the Log P values of Tasigna and its fluorescent derivative are 4.95 and 3.68, respectively). Further analysis showed that the only major difference between Tasigna and Bodipy-Tasigna is within the polar surface area which understandably goes way up for Bodipy-Tasigna. There is no clear data that suggest this should have an effect on passive membrane permeability.
BODIPY® FL Tasigna proved to be an effective tool to study the intracellular Tasigna levels in cells expressing Pgp and ABCG2 with both flow cytometry (Figure 4a) and confocal microscopy (Figure 4b). Since K562 cells do not grow as a monoloayer, but remain in suspension, they could not be analyzed by confocal microscopy. The confocal images were therefore acquired with only HEK cells. K562, K562/i-S9 (Pgp), and K562-ABCG2 (Figure 4a) or pcDNA3.1-HEK, Pgp-HEK, and ABCG2-HEK (Figure 4b) cells were incubated with 0.25 μM BODIPY® FL Tasigna in the presence or absence of different Pgp/ABCG2 inhibitors as described in the Experimental section. While control cells showed high levels of accumulation of BODIPY® FL Tasigna, the Pgp- and ABCG2-expressing cells had low levels of accumulation (Figure 4a and b). Addition of 2 μM Tariquidar (XR 9576, Pgp inhibitor) or 10 μM FTC (ABCG2 inhibitor) completely blocked active efflux of BODIPY® FL Tasigna, thereby increasing total cellular accumulation of the compound (Figure 4b). These results demonstrate that the total intracellular levels of the BODIPY® FL Tasigna in Pgp- and ABCG2-expressing cells are lower than in cells that do not express these transporters, indicating that it is actively pumped out of these cells and that BODIPY® FL Tasigna is a transport substrate for both Pgp and ABCG2. These results substantiate the results shown in Figure 2 suggesting that Pgp- and ABCG2-mediated cellular efflux of Tasigna could be responsible for the decreased intracellular Tasigna levels and its reduced effectiveness at inhibiting BCR-ABL kinase in Pgp- and ABCG2-expressing K562 cells. It should be noted that the difference in total intracellular levels of BODIPY® FL Tasigna in K562 cells (Figure 4a) were modest compared to the HEK cells (Figure 4b). This may be attributed to differences in the expression levels of Pgp and ABCG2 in K562 cells compared to HEK cells (see ref. 41-44).
To demonstrate that the properties of Tasigna are not drastically altered in conjugated BODIPY® FL Tasigna, we characterized its activity in inhibiting BCR-ABL kinase activity. Figure 5a (upper panel) shows that 10-20 μM BODIPY® FL Tasigna inhibited the phosphorylation of Crkl in K562 cells, while total Crkl levels remained unchanged (lower panel) suggesting specific inhibition of phosphorlyation of Crkl. These data suggested that conjugation of Tasigna with the BODIPY group did not qualitatively alter the BCR-ABL kinase inhibitory potential of the parent drug Tasigna. It should be noted that BODIPY® FL Tasigna was less potent than Tasigna in inhibiting BCR-ABL kinase (a potential consequence of the structural alteration of the molecule and/or cytosolic exposure of the conjugate relative to free drug).
To further confirm that BODIPY® FL Tasigna can be used as an surrogate tool to monitor Tasigna's interactions with ABC drug transporters under ex vivo conditions, freshly isolated rat brain capillaries were incubated with BODIPY® FL Tasigna for 1 h. As shown in Figure 5b and c, BODIPY® FL Tasigna was actively effluxed into the lumen of brain capillaries (Figure 5b and c). This could be inhibited by Tasigna and PSC833 or FTC, specific inhibitors of Pgp and ABCG2, respectively. In addition, BODIPY® FL Tasigna also inhibited the binding of 125I-IAAP to Pgp and ABCG2 (Figure 5d), indicating that similar to Tasigna, fluorescent Tasigna also interacts at the substrate binding site(s) on Pgp and ABCG2. These results clearly showed that BODIPY® FL Tasigna is pumped out by Pgp and ABCG2 present at the blood-brain barrier and that this compound interacts with the substrate binding pocket in a manner similar to other typical substrates of these transporters. Consistent with these results, BODIPY® FL Tasigna also stimulated the ATPase activity of Pgp and ABCG2, respectively (data not shown). It should be noted that the IC50 for inhibition of Crkl activity, inhibition of 125I-IAAP binding and the concentration required for 50% stimulation of ATP hydrolysis for BODIPY® FL Tasigna was 5- to 7-fold higher than that for Tasigna. The observed lower activity may be due to the larger size of BODIPY® FL Tasigna (mol. wt. 1108.49) compared to parent compound (mol. wt. 530.18) and/or the altered cellular exposure to the conjugate. BODIPY® FL Tasigna may therefore be especially useful in studies of the interactions of tyrosine kinase inhibitors with Pgp, as this and other TKIs are known to interact with ABC transporters with a higher affinity, making it difficult to observe the TKI transport differences in intact cell assays.
To confirm further that Tasigna is a transport substrate of Pgp, we used polarized LLC-PK1 cells expressing Pgp (Figure 6a) and evaluated ability of these cells to efflux [3H]-Tasigna in transepithelial transport assay (Figure 6b). Cells were incubated with [3H]-Tasigna (64 nM) and drug transport across the cell monolayer was measured for 4 hrs. [3H]-Tasigna transport from the basolateral to the apical compartment (B→A) was significantly higher than transport from the apical to the basolateral compartment (A→B) and a time-dependent linear increase in drug transport across the cell monolayer was observed (Figure 6b). The fold difference in B→A versus A→B [3H]-Tasigna transport at 180 minutes was 5.64 ± 0.44 (Figure 6c). Inhibition of Pgp function with cyclosporine A (10 μM) or tariquidar (1 μM) significantly reduced the B→A transport rate, indicating that the observed transport across polarized LLCPK1 cells was Pgp-specific. Taken together, the results with [3H]-Tasigna and BODIPY® FL Tasigna clearly demonstrate that Tasigna is a transport substrate of Pgp.
Expression of the ABC drug transporters Pgp and ABCG2 has been associated with the development of drug resistance to first generation BCR-ABL kinase inhibitors such as Gleevec 12,40-42.Tasigna, a second generation BCR-ABL kinase inhibitor has been developed as more potent and specific inhibitor that also inhibits the kinase activity of mutant Gleevec-resistant BCR-ABL kinases. Several conflicting reports have been published about the above kinase inhibitors being substrates of ABC drug transporters. While some groups have shown that resistance to Gleevec is due to its low intracellular accumulation 33, 43, 44, other reports have suggested that the resistance is not dependent on drug efflux by ABC drug transporters 45, 46. In the case of Tasigna, it has also been shown that Tasigna interacts with ABCG2 with a very high affinity, is a substrate of this drug transporter, and reverses drug resistance mediated by Pgp and ABCG2 17, 33, while others reported that cellular accumulation of Tasigna in cell lines and primary CD34(+) CML cells is not mediated by active uptake or efflux by major drug transporters and expression of Pgp may not be enough to confer drug resistance to Tasigna 15, 47. However, the nature of the interaction of Tasigna with Pgp is not very well understood. Moreover, the effectiveness of Tasigna in inhibiting BCR-ABL kinase activity in Pgp- and ABCG2- expressing leukemic cells has also not been studied mechanistically.
The data from this study indicate that Tasigna inhibits Pgp activity by interacting with the substrate binding pocket of Pgp, similar to results obtained previously with ABCG2 (Figure 1 and 33). This inhibition of Pgp and ABCG2 function at low micromolar and nanomolar concentrations, respectively, can influence the toxicity or bioavailability of other drugs or metabolites in humans that are substrates of ABC drug transporters. Systemic concentrations of Tasigna after administration of the recommended twice daily dose of 400 mg ranges from 1.7 to 3.6 μM 48. Therefore, the above experimental concentrations of Tasigna can be achieved systemically in CML patients treated with Tasigna, which may further inhibit Pgp physiologically, representing another cellular target for Tasigna that may arise in a secondary phenotypic outcome. Direct evidence for this is presented in our experiments with rat brain capillaries, where Tasigna inhibits Pgp and ABCG2 function resulting in decreased efflux activity of these transporters at the blood-brain barrier.
A fluorescent derivative of Tasigna was synthesized to study its direct interaction with ABC drug transporters (Figure 3 and supplementary information). We showed for the first time that the total intracellular levels of BODIPY® FL Tasigna in Pgp- and ABCG2-expressing cells were lower than in cells that do not express these transporters, indicating that it is actively pumped out of these cells (Figure 4). This efflux of BODIPY® FL Tasigna was inhibited by specific inhibitors of Pgp and ABCG2 in both in vitro and ex vivo assays (Figures 4 and and5).5). This fluorescent derivative also inhibited the BCR-ABL kinase activity although with a lower efficiency that could be attributed to the structural alteration of the molecule, possibly resulting in decreased affinity to its target (Figure 5).
[3H]-labeled Tasigna was also synthesized to test whether it is a transport substrate for Pgp. The polarized LLC-PK1 cells expressing Pgp were used to determine [3H] Tasigna transport. The data clearly demonstrated a net active transport of [3H]-Tasigna from the basal to apical side of the polarized LLC-PK1 cells expressing Pgp and Pgp inhibitors significantly blocked the directional flux of radiolabeled Tasigna (Figure 6). These data validate the results obtained with BODIPY® FL Tasigna. However, Hegedus et al 15, based on an HPLC-MS assay, reported that there was no significant difference in the amount of intracellular Tasigna in control and Pgp-expressing K562 cells (non polarized cells). At present, we do not know the reason for failure to observe transport in non-polarized cells, but most likely it could be the result of high background due to non-specific binding of Tasigna to cells (also mentioned by these authors).
Our results with both the fluorescent derivative and [3H]-Tasigna collectively show that this TKI is transported by Pgp and ABCG2. Based on these data, we conclude that Tasigna is a less potent inhibitor of BCR-ABL kinase activity in Pgp- or ABCG2-expressing drug-resistant CML cells compared to sensitive control CML cells because it is transported by Pgp and ABCG2, resulting in reduced intracellular accumulation. This is an important finding given the clinical application of Tasigna, which is administered to drug-resistant CML and ALL patients. This reduced effectiveness becomes more important in a scenario where the expression of ABC transporters is increased in patients who have been treated with a drug that is a transporter substrate and the incidence of secondary resistance increases because the drug becomes ineffective due to active efflux by these transporters. In fact, despite the initial clinical effectiveness of Tasigna in CML resistant patients, lack of response to Tasigna therapy and development of resistance have also been reported 14, 49.
A non-toxic concentration of Tasigna in combination with the Pgp substrate doxorubicin was able to inhibit drug resistance mediated by Pgp in MDR1-transfected HEK cells (Table 1). These observations could have dual implications in the clinic. Administering Tasigna with drugs that are substrates of Pgp could result in increased systemic concentrations of these drugs. Alternatively, administering Tasigna with drugs that inhibit Pgp function could lead to increased Tasigna toxicity. The FDA summary review for approval of Tasigna reflects these two possibilities, stating that treatment with Tasigna may result in increased toxicity or drug/drug interactions if administered with drugs which are either Pgp substrates or inhibitors (http://www.fda.gov/cder/foi/nda/2007/022068s000_SumR.pdf). Increased oral bioavailability or antitumor response of anticancer drugs in combination with other TKIs such as Gleevec, Gefitinib or Lapatinib has already been shown by a number of studies 50-53.
In conclusion, our findings indicate that interaction of Tasigna with Pgp and ABCG2 may be an important factor in the treatment of CML and AML patients, as efflux of Tasigna by Pgp and ABCG2 may result in resistance to this drug. Moreover, interaction with Pgp and ABCG2 can modify the pharmacokinetic and toxicity profile of Tasigna in vivo. Additional studies to specifically investigate the interaction of Tasigna with ABC transporters may be warranted to determine its efficacy in the treatment of Gleevec-resistant CML and ALL. In addition, BODIPY FL® Tasigna may represent an important tool for researchers to follow the efficacy, pharmacokinetics, and toxicity of Tasigna in preclinical and clinical models. A similar approach may be used to study whether a given TKI is transported by Pgp or ABCG2. It could also be adapted for use in in vivo imaging studies to assess the accumulation of xenobiotics in the brain that are transported by Pgp or ABCG2. To our knowledge, this is the first study that not only demonstrates direct transport of Tasigna by Pgp in transepithelial monolayer assays but also reports synthesis and characterization of a fluorescent derivative of a TKI that is not only active in inhibiting the target kinase but can also be used to study its interaction with other proteins such as ABC drug transporters in cancer cells.
This work was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. We thank Dr. Krishnamachary Nandigama for providing Pgp-expressing High-five insect cell crude membranes, Anne Ramsey for help in kinase assays, and George Leiman for editorial assistance.
Supporting Information (SI). Synthesis and characterization of BODIPY® FL Tasigna and its intermediates. This information is available free of charge via the Internet at http://pubs.acs.org/.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


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forbes.com - 19 readers, 1 Tweets - This article was co-authored by Don Broekelmann, the Executive VP of Brand Management at Influence & Co. There are a lot of definitions of thought leadership floating around these days. People declare themselves thought leaders because they wrote a book or because they have an occasional speaking gig. Thought leadership is [...]


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SiteGiant customers are extremely diverse. From business to personal web sites. Our economical prices make it easy and affordable for anyone to get started on the web without sacrificing quality, reliability, and excellent customer service.
Wonder what our current customers are saying? We can't speak for all of them but here's what a few said (with their permission of course)


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A great had step had now taken by the Supreme Court of India that now all the cinema halls will play National Anthem before the screening of every movie. The regulations notify by the courts on Wednesday and hence give 10 days to all theatres for the application of the same. Accompanying this the Supreme court had also issued the rules, which include screening the national flag on the screen while playing the National Anthem.
The regulation made by the court to regulate the devotion and respect for towards the National Flag and nation as well in people's heart. This step comes in front to get a sense of patriotism and nationalism in people's heart. The court also says that the people should need to respect to their National Flag and National Anthem. The rule is to generate the respect in people's heart and especially in the youth.
Incidence which came in front about the disrespect of National Flag and National Anthem led the court to generate the respect for the same between all. The court also regulates the theatres for attempting the practice which must be accepted by all the theatres withing 10 days. The court had also told that all the people in the theatre should be stand in respect of National Anthem and National Flag.
The court had also ruled the theatres, that it cannot modify the national anthem and can't use any commercial with it. The petition about the same was filled by Shyam Narayan Chouski, who is an owner of NGO at Bhopal.
Before this Maharashtra had notified the theatres to play National Anthem. The step was taken much before in 1960 which gets faded near about 1990's. Stay tuned with us for more updates and news feeds like this.


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USC Academic Honors and Fellowships supports applicants for the following competitive national and international scholarships and fellowships.
Astronaut Scholarship
The Astronaut Scholarship Foundation awards scholarships to college students who exhibit motivation, imagination, and exceptional performance in the science or engineering field of their major.
Beinecke Scholarship
The Beinecke Scholarship Program seeks to encourage and enable highly motivated students to pursue opportunities available to them and to be courageous in the selection of a graduated course of study in the arts, humanities and social sciences (Ph.D. or terminal degree such as MFA).
Boren Scholarship for International Study
Boren Scholarships for International Study, an initiative of the National Security Education Program, provide unique funding opportunities for U.S. undergraduate students to study less commonly taught languages in world regions critical to U.S. interests, and underrepresented in study abroad, including Africa, Asia, Central and Eastern Europe, Eurasia, Latin America, and the Middle East.
Churchill Scholarship
The Churchill Scholarship provides tuition and funding for 14 students each year toward graduate work in engineering, mathematics and the physical and natural sciences at Churchill College, Cambridge University.
Critical Language Scholarship (CLS) Program*
The CLS Program is part of a U.S. government effort to expand dramatically the number of Americans studying and mastering critical foreign languages. Students of diverse disciplines and majors are encouraged to apply. Participants are expected to continue their language study beyond the scholarship period, and later apply their critical language skills in their future professional careers.
Fulbright U.S. Student Program*
The Fulbright U.S. Student Program provides full funding for an academic year of research, english teaching, or internship abroad in over 140 countries for graduating seniors, graduate students and recent alumni who are U.S. citizens.
Gates Cambridge Scholarship
The Gates Cambridge Scholarship is for one year of study as an affiliated student or graduate student at the University of Cambridge. The foundation seeks students to support intellectually outstanding postgraduate students with a capacity for leadership and a commitment to improving the lives of others.
Gilman Scholarship
The Benjamin A. Gilman International Scholarship aims to diversify the kinds of students who study and intern abroad and the countries where they go.
Goldwater Scholarship
Goldwater Scholarships are awarded to outstanding undergraduates who are studying mathematics, natural sciences or engineering and who intend to pursue a research career.
Knight-Hennessy Scholars
The Knight-Hennessy Scholars is designed to build a multidisciplinary community of Stanford graduate students dedicated to finding creative solutions to the world's greatest challenges. Each year the Knight-Hennessy Scholars program will identify a group of 100 high-achieving students from around the world with demonstrated leadership and civic commitment to receive full funding to pursue a wide-ranging graduate education at Stanford University.
Luce Scholarship*
The Henry Luce Foundation seeks to develop a new level of understanding of Asia among future leaders of American society. The program is aimed at students with varied academic backgrounds who demonstrate leadership and have had no prior experience in Asian affairs. The scholarship funds a one-year internship placement in the following countries in East, Southeast and South Asia: Brunei, Cambodia, China and Hong Kong, India, Indonesia, Japan, Malaysia, Mongolia, Philippines, Singapore, South Korea, Taiwan, Thailand, and Vietnam.
Marshall Scholarship
The Marshall Scholarships are available for one or two years of graduate study in most universities in the United Kingdom (England, Scotland, Wales, Scotland, and Northern Ireland). Desired qualities are demonstrated social concern and evidence that a candidate will be a leader both within his or her profession and within the broader community.
George J. Mitchell Scholarship
The George Mitchell Scholarship is a competitive program for individuals wishing to pursue one year of study at one of nine institutions of higher learning in Ireland and Northern Ireland. Desired qualities are demonstrated academic distinction, leadership activity, unselfish service to others, and extra-curricular activity, including potential for future leadership and contribution to society.
Rhodes Scholarship
The Rhodes Scholarship brings students from eighteen countries and five continents to the University of Oxford in England. Study is funded for a one- two- or three-year period. The most important desired quality of a Rhodes Scholar is excellence in the overall academic record, complemented by qualities of leadership, writing ability, social concern, and athletic activity.
Schwarzman Scholarship
The Schwarzman Scholars Scholarship is a highly selective international scholarship program designed to prepare future leaders for success in a world where China plays a key global role. The program will give the best and brightest young leaders from around the world the opportunity to develop their leadership skills through a fully-funded one-year Master's Degree at Tsinghua University in Beijing – one of China's most prestigious universities.
Truman Scholarship
The Truman Scholarship is a competitive and prestigious program for individuals pursuing careers in public service.
Udall Scholarship
The Udall Scholarship awards scholarships to sophomore and junior level college students committed to careers related to the environment, tribal public policy, or Native American health care.
*These programs also welcome applications from recent alumni and/or graduate students.
Beyond this list of opportunities supported by USC AHF, many more competitive scholarships and fellowships are available.


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What is JotForm?
JotForm is a free online form builder which helps you create online forms without writing a single line of code. No sign-up required.
At JotForm, we want to make sure that you're getting the online form builder help that you need. Our friendly customer support team is available 24/7.
We believe that if one user has a question, there could be more users who may have the same question. This is why many of our support forum threads are public and available to be searched and viewed. If you'd like help immediately, feel free to search for a similar question, or submit your question or concern.
How can I reduce the height of my formAsked by artevolve on November 16, 2013 at 06:08 AM
I would like to shorten the overall height of my form without losing any of the elements. There is a lot of space between the various elements that is'nt necessary so it should be possible. I've attached screenshot of my footer to show you the impact the form is having on it ie way too big; btw ive tried using smaller fonts, and reducting height of text boxes etc. There is also space to move some of the titles to the side of the boxes rather than above ee name, email, phone number
At this time I will work on cloned version of your form, once I have made the neccesary changes I will post it back on this thread. Thank you.
Fantastic. Thankyou
Pod Chiropody & Laser
12 Cosby Road
At this time I have injected the tested CSS Code on an example form,
The Injected CSS Code is the following:
.form-input {
position: relative;
bottom: 12px;
#id_4 {
position: relative;
bottom: 22px;
#id_13 {
position: relative;
bottom: 40px;
#id_12 {
position: relative;
bottom: 80px;
#id_2 {
position: relative;
bottom: 100px;
For reference, these are the steps to inject CSS code:
On the Form Editor, select the Setup & Embed, then click on Preferences. On the Preferences window select the Form Styles tab then on the Inject Custom CSS code paste the code provided above.
Kindly check on the Example Form and verify if this is what you need: http://form.jotformpro.com/form/33193470360955 you can also clone the form if needed. I'm proving the steps on how to do so on the related articles section below:
Also, I would suggest to use the iframe code method to add this form to your site.
If you need further assitance, do let us know. Thank you.
Related Articles:
Hi Cesar. Thankyou for the quick response and great information; i have made the change you suggesred and it looks like the screenshot you supplied - just one thing please, the text that starts "APPOINTMENTS, etc can you adjust this so that it is moved down closer to the bottom white box (box 4) at the moment it is too close to box 3; If the text could "sit" just on top of box 4 as it does on the other 3 boxes that should be perfect. Sorrry to bother you and thanks for a great product and fantastic service - better than Mailchimp!
Also, is it possible to stretch all the white boxes so they have the same overall width ie same width as box 4? Thanks
Good to hear we are on the right path. I will work on providing you with the changes you requested. One I have an update on this. I will let you know through this thread. Thank you.
Thats great. You guys sure know about customer service. Bravo!!
I have performed some updates to the CSS code I provided to you earlier, here is the new code:
Here's my example form: http://form.jotformpro.com/form/33193470360955
Do let us know if you need further assistance on this. Thank you.


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SULPHUR — Taking advantage of four Ellender errors, fourth-seeded St. Thomas advanced to the Class 4A semifinals with a 5-1 win Friday afternoon at Frasch Park.
With the win, the Cougars (21-5) advance to play West Ouachita at 1 p.m. Saturday in the Louisiana High School Athletic Association State Softball Tournament .
"We got the runs when we needed them," STM coach Andria Waguespack said. "I'm happy. If you get the chance to play on the last day of the season, then you have had a great season. I'm not going to complain about it. We are going to have to fix some things for (Saturday) but the more important thing is that we get that opportunity to fix some things for tomorrow. You do what you have to do to move on."
STM started the scoring in the bottom of the first. With two outs, Bailey Hemphill walked and Jamie Landry followed with a line drive to center field that was misplayed allowing a run to score. In the midst of the play, a throwing error on catcher Annie Robinson would let Landry score to make it 2-0.
Landry came up big again in the fifth inning. With two runners, she cleared the bases with a two-run triple to increase the STM lead to 4-0.
"I figured that they were going to walk Bailey (again) because she is an amazing hitter," Landry said. "My teammates did their job by getting on base so it was up to me to do my part and drive them in. Bailey is usually our big hitter, and she has gotten the job done for us all season long, but (the Patriots) were not going to let her hit so it was my job to step up and drive in runs."
While Landry led the Cougars, sophomore right-hander Whitney Romero shut down the Ellender attack. She allowing only one unearned run on two hits with 12 strikeouts and two walks.
"The first batter started things off a little shaky for us, but other than that I did feel pretty good about myself in the circle," Romero said. "I always try to bring my best as the games get more and more important and you can't get more important that the state quarterfinals. I pitched with a lot of confidence in the circle.
"Offensively it is always important to capitalize on your opponents mistakes and we were able to do that today.
Waguespack said she continues to be impressed with what her sophomore right-hander brings to the circle each and every game.
"You are talking about kid that shines under the spotlight of pressure," Waguespack said. "She likes to be in the big games, and she likes the big pressure. This is her element. I am happy for her. I'm happy her teammates got her back and played some great defense for the most part. We survived to see another day."
NOTRE DAME 8, BUCKEYE: 2: Elise LeBeouf went 3-for-3 with a home run as Notre Dame defeated Buckeye in a Class 3A quarterfinals.
With the win Notre Dame (19-4) advances to take on top-seeded John Curtis at 1 p.m.
Scoring in every inning but the second, Notre Dame pushed across nine hits. Zoie LaVergne was the other big-hitter for the Pioneers as she drove in two runs on two hits and also scored a pair of runs.
Mollie Stelly was the winning pitcher, striking out four and allowing two runs on four hits and striking out four.
NORTH VERMILLION 13, KAPLAN 4: A seven-run fourth inning propelled North Vermillion to a win over Kaplan in a Class 3A quarterfinal.
North Vermillion (21-6) advances to take on 11th-seeded Jena in a semifinal at 1 p.m. Saturday.
Pounding out 21 hits, North Vermillion was led by the trio of Elise Vincent, Kyla Hebert and Brooke Dupuy who all had 3-for-5 days. Miranda Martin went 2-for-5 and had a homer.
Hannah Yidallier was the winning pitcher, allowing only four hits and striking out two and walking two.
ASCENSION CATHOLIC 6, HANSON 5: Bailey Acosta slid in to score the winning run for ACHS (26-6) after a hit by Kaitlyn Mistretta in the bottom of the seventh. With the win, the Bulldogs advance to play Central Catholic (27-3) at 11 a.m. Saturday.
Raeshaun Malancon hit her second home run of the game to lead off the seventh for ACHS. Bailey Amedee then smashed a triple to set the stage for the Bulldogs to score the winning run. Aimee Prejeant had two hits for the winners. Kim Sonnier (home run) and Paige Diamond (three hits) led Hanson (19-8).
CENTRAL CATHOLIC 9, ST. JOHN 1: Morgan City-based Central Catholic (27-3) scored two or more runs in three innings, got a big day from Landry and got a huge game from Gee Garrett, who had a home run and two doubles.
Seven errors didn't help the cause for St. John (21-13), which lost in the quarterfinals for the second straight year.
Garrett's two-run homer in the sixth keyed a three-run inning that allowed CCMC to put the game away.
Landry, who now has 309 strikeouts on the season, scattered four St. John hits.
"We made it to the tournament last year for the first time in a long time and lost 1-0 in nine innings in the quarterfinals," Central Catholic coach Joe Russo said. "I think we were more relaxed this year. It was our day today. We were on the ball (hitting) and our pitcher had a good day."