text:
How a Running Shoe is Made
How Running Shoes are Made
All running shoes are made by the cold cement construction process. If you want to learn how to design shoes you need to know this basic shoe making process. Cold cement is the modern updated style of shoe construction. Due to the low temperatures required for bonding the upper to the shoe sole, it allows the use of modern lightweight plastic, foam and mesh materials. Every modern high performance running shoe is made by this cold cement process.
Running Shoe Upper Stitching Process:
What are the best materials for running shoes? Most running shoes are constructed with breathable knit Polyester or Nylon mesh. Knit fabric allow the material to smoothly follow the last curves. Running shoe uppers often with PU leather reinforcements. Pu or synthetic leathers are great for running shoes as they have some stretch and are damaged by water. The classic running shoe is made from suede with some mesh inserts. While suede is comfortable and conforming, it's not weather resistant and it's very heavy when wet.
The pattern parts for the shoe are made into steel cutting dies. A cutting die is required for every part and every size. Each shoe part is cut from rolls of fabric or from leather hides. Fabric parts may be layered so many can be cut at the same time. Leather parts must be cut one by one to avoid having scars or other imperfections in the leather show on the final product.
The factories cutting department cuts all the parts for each running shoe, then gathers the parts into kits. One kit for each pair of shoes. After several hundred or even 1000 kits are complete they are passed to the stitching department for assembly.
The stitching department builds the parts of the running shoe sewing then together, finally closing the shoe and adding the tongue.
Running Shoe Production Assembly Process:
The running shoe upper is prepared with the strobel bottom. The outsole covers the edge of the upper so a strobel bottom can be used to make the shoe lighter and more flexible.
The running shoe upper is steamed to soften the materials and the last is inserted and pulled tight. Once the last is tight inside the upper a second lasting machine pulls the heel edge. Once the last is secured inside the upper, temporary shoes laces are pulled tight, and the upper is cooled which allows the upper to shrink and fit tight to the last.
The shoe may have a plastic or fabric part installed on top of the tongue to protect the surface from damage and drift during the lasting operations.
While the upper is being lasted, the sole unit is being prepared. In this case, a rubber sheet sole is combined with the EVA foam cushioning component cemented inside. This is done in a separate process that's called stock fitting.
Running shoe midsoles will be made from weight EVA foam. A thin layer of rubber will allow the EVA to flex, but protect the midsole from wear.
Now that the upper is lasted tightly and the outside unit is compete, the two pieces come together. The rubber sole unit will receive coatings of primer and cement. The outsole will get its own special primer designed for EVA and rubber. The shoe upper is also prepared with its own special primer and cement.
After the contact cement and primer have been completely dried in the heating tunnels, the two pieces are joined together by hand. A skilled worker aligns the upper and outsole together then places the shoe in a hydraulic press.
The running shoe will have 3 pressing operations, usually all done with one machine: a vertical press, toe and heel press, and side pressing. This insures full contact between the upper and outsole uit. Once the shoe is pressed together it's often put in the cooling tunnel to set the glue.
After the cooling tunnel, a shoe de-lasting machine is used to push the last out of the shoe without wrinkling the running shoe upper.
Now the running shoe is complete! At this point you can insert the footbed. The footbed may be molded EVA with a fabric cover or flat sheet cut foam. The flat die-cut footbed is usually cemented inside the shoe, while molded footbeds are most often removable.
The new runner is ready for a final QC inspection – a quick check for any loose threads, cleaning and then packing.
Want to learn more about how running shoes are made? Check out the new book: How Shoes are Made where the shoe making process is described in detail.
learn how to make shoes:Do you want to learn how big brands make shoes? Now you can! How Shoes are Made will show you how modern shoes come to life! More than just a tour through a sneaker factory and more than your average shoe making book! This is the perfect Shoe design a handbook for footwear designers. From drawing shoe designs to sample development and footwear manufacturing, you will learn how it is all done. Written by veteran shoemaking pros, How Shoes are Made will give you a look inside the REAL world of shoe design, development, and mass production. This book teaches shoe making for beginners and students. 220 pages with over 400 color photos and drawings. 26 chapters explaining shoe design, footwear pattern making, sample development, footwear materials selection, upper stitching, outsole and tooling design, shoe lasts, shoe costing, quality inspections, pattern making and much more! A must-read for young shoe designers, sneakerheads, or any footwear fanatic! Secure payments Visa, MasterCard & PayPal. Over 3500 copies sold! Read in over 60 countries!
Ready for Download Now! Edición española See Preview Video On YouTube
Download Now!
Print Edition Now Available!
Table of Contents:The Design Process, Shoe Development, Shoe Patterns, Shoe Specifications, Outsole Tooling, Development Process, Pre-Production, Material Preparation, Stitching Operations, Rubber Pressing, EVA Forming, The Assembly Line, The Shoe Last, Footwear Costing, Importing Shoes, Shoe Logo Design, Leather for Shoes, Textiles for Shoes ,Synthetics for Shoes, Foam for Shoes, Know Your Footbeds, Material Suppliers, Shoe Designers Tools, Jobs in the Shoe Trade ,Quality Control, Starting a Shoe Company, Life at a Shoe Factory, Shoe Making Dictionary
If you want to learn more, check out our new books.
Print Editions and Instant Downloads Available Now!
Shoemaking Books / Go to Shoemaking Tools
How Shoes are Made Download
E-Book edition 220 pages. PC and Mac compatible PDF file. Download Now!
Shoe Material Design Guide Download
E-Book edition 195 pages. PC and Mac compatible PDF file. Download Now!
Start Your Own Shoe Company Download
E-Book edition 170 pages. PC and Mac compatible PDF file. Download Now!
How Shoes are Made Softcover
Print Edition, 250 Pages with over 400 color photos and drawings.
Shoe Material Design Guide Softcover
Print edition 330 color photos, 28 Chapters, 195 Pages order today!
Start Your Own Shoe Company Softcover
Print Edition, 220 pages with over 400 color photos and drawings.
Cómo se hacen los zapatos
El libro va más allá de solo un recorrido por una fábrica de zapatos, y más allá que el típico…
Cómo se hacen los zapatos Descarga digital
Cómo se hacen los zapatos: Una mirada detrás de escena de una verdadera fábrica de calzado deportivo ¿Quieres aprender cómo…
Shoe Designers
Shoe Designers Pack Double Softcover
Two softcover books, paper pattern and Blue Print. Free downloads included!
Shoe Designers Pack Double Download
Two PFD E-books, paper pattern and Blue Print. Download Now!
Sneaker Factory Triple Download
The triple download of all three Sneaker Factory publications.
Start-up your Own Shoe Company
Shoe Company Start-Up Download Plus
E-Book edition 170 pages. Profit margin and Size run calculators. Download Now!
Shoe Company Start-Up Pro Pack Download
A must have for anyone serious about launching a new footwear company!
Shoe Company Start-Up Pro Pack
A must have for anyone serious about launching a new footwear company!


text:
We are excited to be collaborating with numerous groups in Canada and for our upcoming projects in rural and remote regions of the country. In British Columbia, our Faculty and Advisory Committee are widely involved in improving access to surgical care:
Are global surgery initiatives sustainable? A systematic review on sustainability criteria in global surgery initiatives between North American and low and middle-income countries
A research team of junior and senior residents of the UBC Postgraduate Program in General Surgery and staff at Vancouver General Hospital Trauma and Emergency General Surgery have been undertaking a systematic review to comprehensively quantify collaboration in global surgery initiatives (GSIs) between North American and low/middle-income countries since 2000. A total of 3299 published articles on GSIs have been reviewed and included GSIs descriptively analyzed based on publication demographics, surgical subspecialty involvement, and partnership descriptions. An expert consensus has developed a novel model for sustainability criteria of GSIs based on six pillars: multidisciplinary collaboration, bilateral authorship, effective training, broad community engagement, funding/resources, and outcomes reporting. We have identified 134 unique GSIs and counting with ongoing descriptive analysis of collaborations and sustainability criteria met by GSIs. Preliminary results have been presented at the CAGS Canadian Surgery Forum 2017 and UBC Chung Research Day 2017.
Project leaders: Morad Hameed and Emilie Joos
Team: Nicole Jedrzejko, Joseph Margolick, Morad Hameed, Emilie Joos

subset: commoncrawl


text:
Owner Interview: Chinese Cast Bronze Guardian Figure, ca....
Clip: Season 16 Episode 3 | 1m 41s
Hear more from Max, the owner of the Ming Dynasty cast bronze figure that was appraised in Tulsa for $75-$100,000!
Aired: 01/15/12
Problems Playing Video?
Funding for ANTIQUES ROADSHOW is provided by Liberty Mutual Insurance, Ancestry, and Consumer Cellular. Additional funding is provided by public television viewers.


text:
See THIS LINK
Incidentally, the Wallingford Screen in the Abbey is due to a 15C William of Wallingford.
See THIS LINK
Gorhambury, about 2½ miles NW of St Albans, was the country seat of Francis Bacon (1561-1626). His father built Old Gorhambury House in 1563-1568 and Francis lived here from 1568. He was a student at St Alban's school. He inherited the old house in 1601, enlarged and rebuilt it and then built a summer house, Verulam House, about a mile away. After his fall from power in 1621, he retired here. A doorway and some walls of Old Gorhambury House survive, but nothing remains of Verulam House. His tomb (or monument) in St Michael's Church has a figure of him. Some guidebooks say he is buried in the vault underneath. The present Gorhambury House was built by the Earl of Verulam, a collateral descendent, in 1784 and is occupied by the current Earl. It is open and displays various memorabilia. [Crosland]; [Glendinning]; [Eastman]
See THIS LINK
Lord Grimthorpe, designer of the clock at Parliament (cf under London), restored the west front of the Abbey in the late nineteenth century. His restoration work was not always well received, particularly here and at Lincoln's Inn, and 'to grimthorpe' was used for 'to do a rotten job of restoration' [Espy].
H.T. Flather, the crystallographer who built the "very beautiful set of miniature models of all the fifty-nine (stellations of the icosahedron)" was living in St Albans when he offered the models to the University of Cambridge and Coxeter came to see them. [Coxeter, Du Val, Flather & Petrie].
See THIS LINK
To see an Ordnance Survey map click at THIS LINK
|Previous entry
|Next entry
|Gazetteer Index
|Map form of the Gazetteer index
|Main MacTutor index
An extract from The Mathematical Gazetteer of the British Isles created by David Singmaster
The original site is at THIS LINK


text:
Do You Love OREO's & Chocolate? Check Out The OREO Chocolate King Size Candy Bar Rollback Giveaway! Ends 4/27
This post was sponsored by Nabisco as part of an Influencer Activation for Influence Central and all opinions expressed in my post are my own.
Yes… it is true! Delicious & Chocolatey OREO Chocolate King Size Candy Bars are now on Rollback at Walmart! They are so delicious and honestly… if you love OREO's and Milka Chocolate…. then you are going to absolutely love the combination of the two in a delicious candy bar. Milka Chocolate bars are a true favorite around the world and OREO, of course, is Milk's favorite cookie…. so you know that the two are the perfect fit. Right now OREO Chocolate King Size Candy Bars are on Rollback at Walmart so make sure snag a few on your next trip… for just $1! There are two bars in each King Size pack and I love that each bar is individually wrapped… so you can enjoy one now and another later. The only question is….. which flavor is your favorite? Original or Mint?
My daughter and I love the original flavor best, but my husband… definitely loves the mint flavor. They are both really delicious and the combination of dunkable OREO cookies, vanilla rich crème (or mint) all covered in delicious chocolatey goodness…. are sweet perfection. We love them for sure and I toss one in my husband and kids lunch occasionally as a sweet treat. These are a great treat and a great gift for that chocolate lover in your life too as Milka Chocolate is creamy and delicious and a favorite for sure. Make sure that you take advantage of this sweet Rollback at Walmart for a $1.00 now… try each flavor and then tell me which is your favorite as they are both so good.
OREO Facebook ~ OREO Twitter ~ OREO Pinterest ~ OREO Instagram
Make Sure You Snag Some For Just $1.00 And Enter The Giveaway Below To Be 1 of 7 Lucky Winners To Win Walmart Gift Cards!
Prizes: 1 $200 Walmart Gift Card Grand Prize and 6 $50 Walmart Gift Card Prize Winners
Dates: Monday, April 9th – Friday, April 27th
I-C will randomly select 7 winners from all program entries and will facilitate fulfillment of the 7 winning prizes.
Enter Today & Good Luck!
OREO Chocolate Candy Bar Sweepstakes
Deliciously Savvy is not responsible for the prize fulfillment.
As Always, Thank You For Visiting Deliciously Savvy Today & Leave Some Comment Love Or Enter Another Giveaway While You Are Here. I Always Love To Hear From You!


text:
The shedding of hair is a normal and ongoing process for most domestic dogs and cats.
Excessive shedding generally occurs in the spring and fall with the changing of major seasons. Old hair is released so that new hair of the right consistency and insulation factor may grow in.
In the winter, hair fluffs up to provide insulation from the cold. For this reason, matted hair does not protect a dog or cat from the cold. Many pets (especially the cold weather breeds like Elkhound, Huskies or Samoyeds) also have an undercoat of soft downy hair to protect them from extreme cold. In the summer, hair can also function to protect pets from overheating by insulating against the heat of the sun.
Since most pets spend at least part of their time indoors, and are often exposed to both air conditioning and heating systems, their bodies may begin to start shedding hair year round.
Shedding is best controlled by regular grooming, either by bruthing at home or with professional grooming services, or a combination of both. Keep in mind that regardless of how much hair might be removed at a grooming shop, even with special products, nothing will remove all the loose hair and give you back a non-shedding dog.
Hair is also shed whenever a pet is nervous or excited. You have probably noticed that your pet sheds more than normal during a visit to the vet. This is because the pet's nervousness causes the skin to tighten, which forces out any loose hair. And when you pick him up from the groomer, the same thing occurs – his excitement loosens up hair that was not able to be removed (or ready to be shed) during the grooming process.
Some diseases can promote poor hair growth and shedding. If your pet experiences unexplained hair loss, or you suspect there may be a medical condition causing the excessive shedding, it is always wise to consult a veterinarian.
Good diet, regular brushing and special attention during spring and fall shedding seasons will help keep extra hair off your clothes and floors.
A good quality oil supplement can be added to your pet's food, such as any fish oil or omega 3 & 6 which can help replenish lost moisture in the skin and reduce shedding. These products are sold in better pet food stores.
Please do not hesitate to ask me if you need suggestions on which tool to use to de-shed and brush your pet's coat.
Non-Shedding Coats
Breeds with a non-shedding or low shedding coats have become very popular in the last few years. These range in size from very small to very large, such as the Toy Poodle, Yorky, Maltese, Lhasa Apso, Shih Tzu, Bichon, Havanese, Cotton de Tulear, Chinese Crested Powderpuff, Miniature Schnauzer, Tibetan Terrier, Lowchen, West Highland Terrier, American Cocker Spaniel, Portuguese Water Dog, Bouvier Des Flandres, Standard Poodle, Airedale and many more .
Non-shedding dogs do not shed their coat twice a year, although there is some coat loss – similar to our own hair loss if you will or in some cases, a degree of shedding may occur in cycle. Their coat continually grows; these breeds require regular clipping and grooming. Some dogs have a cottony texture coat and tend to tangle easily. For example, some Shi Tzus have a cottony coat that tangles easily while others Shih Tzus never get any tangles. Much like humans or members of the same family, dogs of the same breed can have very different hair texture.
Most non-shedding breeds must be brushed and combed every few days. If you have wall to wall carpet, the static electricity, especially in Winter when the furnace is on, can create mats or tangles on the legs, underbelly, chest and rear of the dog. Those dogs with a silky or coarse coat don't tend to be affected by static as much.
Most non-shedding breeds look very cute in a puppy cut, which is easier to care for but they can also be kept in a longer clip. Breeds such as the Yorkies or Maltese look beautiful with styles, short of long.
I personally use a good quality re-moisturizer in the Winter months to keep the coat soft and hydrated.
If you have a non-shedding breed, I recommend grooming every 6 to 8 weeks, depending on the coat texture and thickness.
Some customers choose to have a bath/dry every 4 weeks, alternating with a full groom (so once a month, a bath and the following month, a groom). Full bath/dry, eyes and anal area is $20.
Regular grooming will benefit both you and your dog: he or she will always smell good, look and feel great.
If you are unsure on which brush or comb to use, do not hesitate to ask, it will be my pleasure to show you the proper technique and equipment to keep your dog's coat free of tangles, soft and clean.


text:
[Fixed] hydra 7.4.2 for windows
Sorry for the late update, as promised i will try to keep this updated to the last version as possible.
Hydra is A very fast network logon cracker which support many different services like Samba, FTP, POP3, IMAP, Telnet, HTTP Auth, LDAP, NNTP, MySQL, VNC, ICQ, Socks5, PCNFS, Cisco and more
You can download the hydra tool here hydra-7.4.2-windows.zip compiled for windows and it includes the cygwin DLL's so you don't have to download it yourself.
You can download the source here hydra-7.4.2.tar.gz
UPDATE: I fixed the error, please re-download.


text:
"The result of this trial speaks for itself!"
This often heard phrase contains a troubling assumption: That an experiment can stand entirely on in its own. That it can be interpreted without reference to other trials and other results. In a couple of articles published over the last two weeks, my co-authors and I deliver a one-two punch to this idea.
The first punch is thrown at the US FDA's use of "assay sensitivity," a concept defined as a clinical trial's "ability to distinguish between an effective and an ineffective treatment." This concept is intuitively appealing, since all it seems to say is that a trial should be well-designed. A well-designed clinical trial should be able to answer its question and distinguish an effective from an ineffective treatment. However, assay sensitivity has been interpreted to mean that placebo controls are "more scientific" than active controls. This is because superiority to placebo seems to guarantee that the experimental agent is effective, whereas superiority or equivalence to an active control does not rule out the possibility that both agents are actually ineffective. This makes placebo-controlled trials more "self-contained," easier to interpret, and therefore, methodologically superior.
In a piece in Perspectives in Biology and Medicine, Charles Weijer and I dismantle the above argument by showing, first, that all experiments rely on some kinds of "external information"–be it information about an active control's effects, pre-clinical data, the methodological validity of various procedures, etc. Second, that a placebo can suffer from all of the same woes that might afflict an active control (e.g., the "placebo effect" is not one, consistent effect, but can vary depending upon the type or color of placebo used), so there is no guarantee of assay sensitivity in a placebo-controlled trial.
The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.


text:
Hoyo De Manzanares And Madrid Railway Relics, Spain, 2015
The City Council, because of the wonderful outcomes of the put in gear, has decided to keep our EUROSONDELCO system and combine it with our new DURGAS system for all new contracts for complete maintenance of the present 100km of underground tunnels. Home911 helps you immediately join with native professionals who are on name and able to help 24/7. The Firm has roughly 10.000 customers. Full range of plumbing providers and specialising in boiler and radiator installation. The HomeAdvisor Neighborhood Ranking is an overall rating primarily based on verified evaluations and suggestions from our group of house owners that have been connected with service professionals.
Your residence's Madrid, Iowa HVAC system may require a wide array of distinctive providers to be as dependable, useful, and gas environment friendly as is feasible. It's a simple course of, however it changes depending on what stage of the repair you're at. In case you've signed up for either choice and we haven't started any work you have got a 14-day cooling off interval which starts the day we deliver any parts, or the day you accept our quote (if the job wants labour however no parts).
Remark: wall unit furnace will work when pilot is re lit however has gone out twice now so one thing needs to be executed pilot stayed lit then I cleaned it after it began the first time and it went out and it retains occurring, must have hit one thing? About 540,000 suppliers, producers, distributors and repair suppliers get in touch with 1.three million consumers each month on , and"
We offer an economical path to marketplace for business homeowners and their representatives and a one cease store for aspiring entrepreneurs and enterprise patrons. Although it is a risk to change a single portion of a normal Madrid HVAC system, such HVAC companies in Madrid, IA normally should not encouraged due to the assorted points which might come up as soon as the outdated HVAC Madrid network operates alongside a proficient, more recent set up.
It is time to quote out a new heating system. The business case of the typical service is incredible: the total gross revenue per average installation: is over 30% Does your furnace have a hard time keeping your private home or enterprise warm? Whether or not you might be in need of service next week, or emergency service right now, our educated and qualified plumbing professionals are right here that can assist you.


text:
Jose Mourinho fielding a weakened Manchester United side to take on Arsenal this weekend would be against the spirit of the Premier League, says Martin Keown.Jurgen Klopp speaks out on Liverpool's deal for 'very good player' Takumi Minamino
The former Gunners defender was not impressed to hear that the United boss was considering resting some big names for this Sunday's clash at the Emirates Stadium due to prioritising the Europa League.
Arsenal against United is always one of the league's biggest fixtures, even if it has taken on slightly less significance in terms of the title race in recent years, and Keown isn't convinced Mourinho will end up sticking to his word.
'It is not in the spirit of the competition if Jose Mourinho fields a weakened team against Arsenal,' Keown wrote in the Daily Mail.
Manchester United's remaining fixtures
Crystal Palace (H) - Sun 21 May
Ajax - Europa League (N) - Wed 24 May
'We pride ourselves that there are no easy games in the Premier League.
'United are just a point outside the top four. Regardless of whether they win the Europa League, I cannot imagine United would want to throw away all their season's work in the league. Doing so would give Arsenal an outside chance of breaking into the top four and I cannot believe that Mourinho is willing to give Arsene Wenger a leg-up.
He added: 'If United want to give up on fourth then that's up to them, but this could all be smoke and mirrors from Mourinho.'
MORE: Surprise Man Utd star is now their most important player, says ex-Gunner
MORE: Messi, Suarez and Neymar take their season tally for Barcelona to 100 goals


text:
As some sources are mentioning a history of lean thinking is rooted several hundreds years back all the way to the Venice in 16th century where a first written trace of the "moving" assembly line could be found.
This video gives very brief overview of some of the important events and people in the history of the lean management such as:
This video doesn't give detailed overview of the History of Lean but only a brief introduction.
The video ends with the description of how lean is implemented in service industry as well.
Watch the video and share your thoughts and opinion in the comment.


text:
Demonstrating against coal-fired power, nine Greenpeace protesters scaled a 150 metre high chimney stack at Huntly Power Station, in New Zealand's North Island yesterday. It appears the protestors did some minor damage to the stack.
I wonder what they are trying to prove with these puerile, illegal stunts. Their cause may be good, but their actions will do a lot to alienate much of the public from the entire environmental agenda – well, that's what I think. As the spokesman for the power company puts it:
There are 1.3 million people who get their power from this station in the upper North Island and if we cut this station off now there would be a lot of people who [will be] cold and in the dark this winter. SourceIt's all part of the politicization of the environment. We need to recognize that we are all beneficiaries of the damage that power plants and much other infrastructure do to the environment. We are all in this together. Sure, the protestors probably do have a smaller environmental 'footprint' than most of the rest of us. But they need us on their side if we are to improve environmental outcomes – as against the media profile of Greenpeace. Stunts like smack of sanctimony and smugness. They don't help.


text:
Year: 2011
Place: Florence
State: Project
Team: Arch.I.E.Terruzzi
Client: Private
"Premio nazionale di bioarchitettura 2011" competition – This system has been designed so as to allow winter sunlight into the building and to shield the summer sunlight. The winter sun exposure can thus be stored in a massive wall placed behind the glazing, contributing in a passive way to the heating of the building. In summer the chiaroscuro of circular wood elements softens the reflective effect that you would have looking from the inside to the outside light.


text:
In the course of wrapping up at Binghamton, I've needed to save quite a bit of professional e-mail, mainly correspondence related to presentations, articles, the list I manage. I also want to maintain several discussion list subscriptions that I've had through my work account.
So, I set up a new Gmail account just for professional but not strictly work-related e-mail, and boy, do I wish I had done it a long time ago! I would have saved myself the hassle of having to print, save, or forward messages that I now want to keep beyond my tenure at BU. And, more important to work productivity, traffic from several high-volume lists is now diverted from my work account, significantly lowering the e-mail distraction factor. Although I felt ambivalent about having yet another e-mail account, it's worked out very well and I highly recommend the strategy.
I'm in the process of setting up an e-mail form (and some other stuff) on this site, so stay tuned if you want to contact me.


text: tag:blogger.com,1999:blog-8574338067530390181.post2631680909362470497..comments2019-12-04T00:13:39.072-08:00Comments on Rabbit LLC - Denver Adwords PPC, SEM, SEO, and Design: Indian Wedding Elephant Art - Free Desktop email@example.com:blogger.com,1999:blog-8574338067530390181.post-46522296101340611412018-01-13T14:00:09.305-08:002018-01-13T14:00:09.305-08:00I`m Charlie Bean and I live in Toronto Canada. I n...I`m Charlie Bean and I live in Toronto Canada. I needed a loan to buy a house and I searched for a mortgage loan from all banks and I was denied and I loss hope of having my own house until I came across a post just as you reading my post now. I saw a post about a Financial Service Company who gives loan at 2% interest so I applied in STEAKLEY FINANCIAL SERVICES using their email firstname.lastname@example.com. And my loan was granted it was like a dream but was true and now am a owner of a house in Toronto and am paying the mortgage loan with no stress and I also requested if I can be granted a business loan and I was also granted. Now am living a happy life, I will advice you if you have an financial problems and you need money to settle it so you can pay with no stress just contact Steakley Financial Service at their email email@example.com or number +1(512) 714-8010.Charlie Beanhttps://email@example.com:blogger.com,1999:blog-8574338067530390181.post-14839010429233004662016-05-10T03:52:16.268-07:002016-05-10T03:52:16.268-07:00Very cute!! Try out free vector download source fo...Very cute!! Try out free vector download source for your blog. I download there a lot of images I needed for my web site.Sandra Woodshttps://firstname.lastname@example.com:blogger.com,1999:blog-8574338067530390181.post-30802353806913431872015-07-30T03:02:37.314-07:002015-07-30T03:02:37.314-07:00Mr. and Mrs. Kessel had great fun incorporating a ... Mr. and Mrs. Kessel had great fun incorporating a bicycle into their special day. Mike told us, "My wife and I were delighted to ride off in such a unique manner. Also, our guests were impressed that we didn't fall down." kad kahwinElizabeth J. Nealhttps://email@example.com


text:
October 1, 2017
- Tips on successfully hosting USTA tournaments
- Host Xpress Tournaments for entry level 8 junior players.
- Host a Tennis BASH – a simple, clearly defined, turn-key and consistently fantastic entry-level tournament experience! Find out more and fill out the form and send it to Rob Issem.
Pay Player Fees
Junior Tournament Resources
USTA Mid-Atlantic has created these tips and resources to help you get familiar with the different levels of play and the player pathway as it relates to establishing effective tournaments. Find information on regulations, level, recommended entry fees, duration, match format and draw formats. Please review this information to best prepare for your tournament.
- Mid-Atlantic 2017 Junior Tournament Pathway Tournament Guide
- Mid-Atlantic Junior Pathway Explained
- Mid-Atlantic Junior Tournament Regulations and Point Tables (2017)
- Mid-Atlantic Junior Tournament Regulations and Point Tables (2018)
- Grants are available for entry level tournaments!
- Mid-Atlantic Tournament Resource Library
Net Generation
All youth tournament directors in the Mid-Atlantic Section are required to be fully Safe Play approved on netgeneration.com. ADVERTISEMENT By joining the Net Generation as a provider, you'll help the USTA create fun and safe opportunities for kids to learn and play tennis. You'll also gain access to educational tools and resources to help you take your coaching and organization to the next level. For specific questions, please contact Bonnie Vona.
Adult Tournament Resources
Get Started Hosting Tournaments
Now that you reviewed all the resources, take the following steps for success hosting tournaments for juniors or adults.
- Complete a TD agreement
- Review the Easy Sanction Form and complete a Sanction Application – junior tournaments only
- View the webinar to learn to use the tournament data manager program
Post Tournament Resources
Your event is complete; there's just a few last steps to finish things up!
- Email a tournament evaluation to all participants
- Remit tournament player fees to USTA Mid-Atlantic
- Copy the sanction application to next year and submit for approval
General Tournament Resources
USTA Officials training resources
Tennis rules and regulations and the USTA Friend at Court


text:
Mycozil Review
by Jency William (2019-04-17)
The first thing that you should consider Mycozil when in the search for proper pain medication is your doctor's advice. It would be wise to consult with your doctor or with a trusted physician first before you decide to start any kind of pain medication either orally or topically. Consulting with your doctor not only assures safety but also the possibility of choosing the best type of relief for your kind of pain. Also, consulting with your doctor is a must when you are under another treatment or if you are pregnant. The type of pain can also be a good factor to consider when choosing pain medication or relief. There are some kinds of pain relievers which work best for certain pains as well a pain relievers which work best in a certain form (ointments, creams, tablets, etc.). With the usual muscle or joint pains, many prefer to use topical ointments compared to those taken orally. Another big consideration is whether to take natural pain relief remedies or chemical-based ones. This is very important to many especially to those who would rather use products that are nearer their natural form. For instance, there are 100% natural pain remedies that are made from essential oils and which are not diluted. This kind of pain remedy is more effective than those which only contain a small percentage of the pain relief extract.


text:
Mini Review ARTICLE
Neutrophil Integrins and Matrix Ligands and NET Release
- 1Division of Surgical Research, Department of Surgery, Rhode Island Hospital, Providence, RI, USA
- 2Warren Alpert Medical School, Brown University, Providence, RI, USA
Neutrophils are motile and responsive to tissue injury and infection. As neutrophils emigrate from the bloodstream and migrate toward a site of affliction, they encounter the tissue extracellular matrix (ECM) and thereby engage integrins. Our laboratory studies the neutrophilic response to the fungal pathogen Candida albicans either in the filamentous state of the microbe or to the purified pathogen-associated molecular pattern, β-glucan. We have gained an appreciation for the role of integrins in regulating the neutrophil anti-Candida response and how the presence or absence of ECM can drive experimental outcome. The β2 integrin CR3 (complement receptor 3; αMβ2; Mac-1; CD11b/CD18) plays an important role in fungal recognition by its ability to bind β-glucan at a unique lectin-like domain. The presence of ECM differentially regulates essential neutrophil anti-fungal functions, including chemotaxis, respiratory burst, homotypic aggregation, and the release of neutrophil extracellular traps (NETs). We have shown that NET release to C. albicans hyphae or immobilized β-glucan occurs rapidly and without the requirement for respiratory burst on ECM. This is in contrast to the more frequently reported mechanisms of NETosis to other pathogens without the context of ECM, which occur after a prolonged lag period and require respiratory burst. As expected for an ECM-dependent phenotype, NETosis and other neutrophil functions are dependent on specific integrins. The focus of this review is the role of ECM ligation by neutrophil integrins as it pertains to host defense functions with an emphasis on lessons we have learned studying the anti-Candida response of human neutrophils.
Prevalence and Risk Factors for Candidiasis
Candida albicans exists as normal flora of the skin and GI tract but can become a serious and life-threatening infection. Candidiasis can present either locally as mucocutaneous infection or as the more severe invasive form of the disease. Predisposing factors lending to loss of host control of the colonized organism are likely to be a combination of host as well as microbial factors (1). Invasive candidiasis continues to be a significant medical problem and Candida ranks as the fourth leading pathogen in causing nosocomial infection with mortality up to 40% in spite of available anti-fungal therapy (2). Infection can take place in any bodily organ and systemic infection can involve coincident infection of multiple organs, as well as the blood.
Clinical risk factors for acquisition of Candida infection include neutropenia or a neutrophil defect whether heritable or epigenetic, systemic antibiotic usage, central venous catheter, mucosal damage, and prolonged stay in the ICU even in the presence of surfeit neutrophils (3, 4). Candida infection is remarkably high in non-trauma emergency surgical patients with a prolonged ICU stay, reaching a rate of 21.7/100 discharges, higher than other established high-risk populations (5, 6).
Fungal Recognition
Candida albicans is a polymorphic fungal pathogen that can grow as yeast, pseudohyphae, and true hyphae and the ability to switch between phenotypic states is an essential virulence factor complicating immune detection (7–9). Neutrophils respond to infectious fungi in a variety of ways, including phagocytosis, production of reactive oxygen species (ROS), degranulation, recruitment of other leukocytes, and the more recently recognized release of neutrophil extracellular traps (NETs). In its budding yeast form, C. albicans is small enough for neutrophils to phagocytose. This response involves uptake of microbes into the phagosome, where fusion of cytotoxic granules and oxidative products facilitate microbial killing (10). The invasive filamentous forms of C. albicans are too large to be engulfed, necessitating other cellular strategies for anti-fungal response and clearance (11–16). The recently described process of NETosis, where NETs consisting primarily of DNA studded with histones and components of cytotoxic granules are extruded into the extracellular space, accomplishes the dual functions of both immobilizing and killing harmful microbes where phagocytosis is not feasible (17).
Innate immune cells recognize C. albicans by binding to molecules present in the fungal cell wall. β-glucans are a class of long-chain polymers of glucose in β-(1,3) (1,6)-linkages that are conserved in microbial structures but not found in mammalian cells and, thus, are considered a pathogen-associated molecular pattern (PAMP) (11, 18, 19). Pattern recognition receptors (PRRs) on cells of the innate immune system discern PAMPs as being non-self and initiate antimicrobial host defense mechanisms through activation of intracellular signaling pathways. With regard to recognition of β-glucan, two receptors have received the most attention; the integrin CR3 and the C-type lectin Dectin-1 that may exert non-overlapping roles in clinical and experimental host defense. To parse the relative roles of these receptors, one must take into account the species of the host and immune cell type being studied as the anti-fungal role of these receptors can differ between monocyte/macrophages and neutrophils. Differences may also lie in the specific immune function being assayed and the morphological form of the Candida.
Dectin-1 plays a key role in C. albicans control in mice such that mice defective in Dectin-1 are susceptible to fungal infections while CR3 knockout mice are more resistant to challenge with disseminated C. albicans, suggesting that CR3 has a non-protective, or suppressive effect on murine host defense (20). In humans, Dectin-1 has been shown to be important in control of mucocutaneous but not systemic infection (21, 22). This was supported by a study of a family with a mutation of caspase recruitment domain-containing protein 9 (CARD9), a signaling molecule downstream of Dectin-1 (23). In this family, the CARD9 defect presented as a predisposition to mucocutaneous candidiasis similar to the absence of Dectin-1, mediated by a cytokine production defect of monocytes and macrophages (21, 23). Neutrophils from leukocyte adhesion deficiency (LAD) type 1 patients that are devoid of CD11b/CD18 but which express Dectin-1 failed to internalize Saccharomyces cerevisiae or unopsonized zymosan demonstrating the primacy of CR3 in phagocytosis of unicellular yeast and β-glucan-containing particles (24). In short, phagocytosis of unopsonized yeast or β-glucan-containing particles is primarily mediated by CR3 in human phagocytes and by Dectin-1 in murine cells (25). It is not clear why the genetic absence of CR3 has such different implications for anti-fungal immunity in mice and humans. This is often correlated with the notion that CR3 ligation by β-glucan particles fails to induce respiratory burst thereby limiting this host defense mechanism (26). However, we and others have shown that human neutrophils induce a CR3-dependent respiratory burst to fungal hyphae or immobilized purified β-glucan as a model of the response to non-phagocytosable filaments (11, 12, 15). Given the multifaceted role of CR3 in immune response to a pathogen, it is difficult to ascribe a mechanism to the increased resistance in CR3 knockout mice.
With regard to recognition of non-phagocytosable fungal hyphae, our laboratory showed that antibody blockade of either fungal cell wall β-glucan or neutrophil CR3 was sufficient to obviate the respiratory burst of human neutrophils; antibody blockage of Dectin-1 had no effect (11, 13). In addition to the host defense mechanisms affected by CR3 and Dectin-1 individually, there is solid evidence for a crosstalk pathway connecting these PRRs. Li et al. showed a mechanism dependent on the RhoGTPase exchange factor, Vav, through which binding of β-glucan to Dectin-1 resulted in CR3 activation in both murine and human cells (27). This highlights the potential complexity of working toward a more complete understanding of the differential nature of immune recognition of C. albicans hyphae and yeast forms. A significant step forward in this regard is found in a report by Lowman et al. (22) in which a novel cyclical, or "closed chain" structure of β-glucan was found in C. albicans hyphae but not in yeast. These authors purified β-glucan from C. albicans yeast and hyphae into water-insoluble microparticulate form and showed that the β-glucan extracted from hyphae, but not yeast, produced a potent IL-1 response by human monocytes and macrophages, which was Dectin-1-dependent. Whether monocyte Dectin-1 can recognize cyclical hyphal β-glucan within the cell wall of the organism remains to be seen. Findings to date suggest that Dectin-1 recognition of Candida hyphae is limited to bud scars where β-glucan is particularly exposed, it does not appear to recognize β-glucan along hyphal filaments (28). Whether neutrophils exhibit differential responsiveness to these β-glucan isoforms has not yet been determined. Therefore, the differential responsiveness of innate immune cells to the yeast and hyphal forms of C. albicans may well be due to variance in the structure of the prominent fungal PAMP β-glucan. Work from our laboratory and others show that CR3 is most likely the prominent immune receptor on human neutrophils and is able to detect β-glucan within fungal filaments (11, 13, 15, 29). As CR3 serves as both a PRR and an extracellular matrix (ECM)-binding integrin, it plays a critical role in integrating tissue environment and microbial recognition, driving neutrophil anti-fungal immunity.
Role of Integrins in Anti-Fungal Immunity
All cell–cell and cell–ECM adhesive events occur extracellularly but are translated into cellular responses by communication across the plasma membrane through the action of integrins (30). Integrins are essential for proper regulation of a number of fundamental physiological processes, including tissue morphogenesis, inflammation, immune responsiveness, wound healing, and regulation of cell growth and differentiation. All cells express a contingent of integrins and respond to integrin activation by cytoskeletal-dependent processes, such as shape change, adhesion, spreading, migration, and/or phagocytosis (31). Among 24 αβ heterodimers that have been reported in vertebrates, the β2 family (αLβ2, αMβ2, αXβ2, and αDβ2) are specifically expressed on leukocytes (31). Leukocyte β2 integrins regulate many aspects of immune or inflammatory responses because, unlike cells that reside within solid tissues, circulating leukocytes by necessity relocate during the course of immune reactions. In so doing, they dynamically adhere and de-adhere to cells of the vasculature, to other immune cells, and to components of the ECM, in order to ultimately contact the foreign body or pathogen at the site of infection or injury. Evidence for the physiological significance of leukocyte integrins is highlighted by the recurrent, life-threatening infectious episodes observed in LAD patients that are genetically deficient for expression of β2 integrins (32). In stark contrast to impaired host defense found in the absence of β2 integrins, sustained and improper activation of these integrins contributes to the pathogenesis of autoimmune diseases, chronic inflammatory disorders, and ischemic stroke (33).
Complement receptor 3 (CR3; αMβ2; CD11b/CD18; Mac-1) is a member of the β2 integrin family, yet it functions like no other integrin and, in some ways, like no other receptor yet described in nature. In general, receptors can be defined as having a canonical ligand that binds with characteristic affinity to a single binding site which, in turn, leads to a characteristic intracellular response. In stark contrast, CR3 has two spatially distinct binding sites, the so-called I-domain and the lectin-like domain, that bind completely different ligands and results in differing cellular responses. The I-domain itself is a highly promiscuous binding site with over 30 structurally unrelated ligands shown to be capable of binding at that domain alone, including iC3b, fibrinogen, ICAM-1, fibronectin, heparan sulfate, and factor X (34, 35). I-domain ligands are both host- and microbial-derived such that a multitude of immune effector functions executed by inflammatory neutrophils are entirely mediated, or regulated, by CR3. As with other integrins, ligand binding is regulated by the structural state of activation such that when in a bent conformation the integrin is in a low-affinity state that is modulated upon activating signals that can originate internally (inside-out) or externally (outside-in). In either case, the receptor assumes an upright conformation consistent with high-affinity ligand binding that can be further regulated by receptor clustering resulting in avidity modulation (36). The lectin-like domain is spatially distinct from the I-domain, and is noted for its ability to bind the glucose polymer β-glucan (11, 18, 37–39). Ligation of purified fungal β-glucan to CR3 is sufficient to induce a signaling response (39). The ability of CR3 to mediate neutrophil recognition of fungi and initiate signaling identifies it as the only integrin that also serves as a PRR.
A novel aspect of CR3 bioactivity is that the manner in which it is ligated at its two binding domains has a profound effect on cellular responsiveness. This concept was first posited where Vetvicka et al. reported that murine and human natural killer cells could acquire cytotoxic capability for resistant tumor cells if targets were opsonized with iC3b, a well-described CR3 I-domain ligand, and effector cells were exposed to β-glucan, but not by either ligand alone (40–42). This increased cytotoxic activity could be inhibited with CR3-specific antibodies. Administration of β-glucan enhanced the activity of complement-fixing, anti-tumor antibodies in vivo, causing tumor regression and increased survival as compared to mice receiving either antibody or β-glucan alone (43–45). Surprisingly, this adjuvant activity of β-glucan in reducing tumor burden was shown to be mediated by neutrophils and did not occur in mice lacking either CR3 or complement or in mice depleted of neutrophils.
Role of Extracellular Matrix in Anti-Fungal Immunity
In a seminal paper by Carl Nathan in 1989, the respiratory burst of human neutrophils to soluble proinflammatory mediators was shown to be adhesion dependent and require attachment to either ECM components or human umbilical vein endothelial cells (46, 47). This adhesion dependence of neutrophil effector function provided an early the basis for suggesting the coordination of integrin and non-integrin stimuli to drive host defense in tissues. As CR3 mediates cellular interactions with ECM, and since all neutrophilic responses to tissue infections necessitate ECM contact, we focused our attention on investigating the role of CR3 as a fungal PRR via the lectin-like domain in the presence of fibronectin, a ubiquitous ECM molecule and I-domain ligand. We showed that the effect of CR3 on the anti-fungal response of human neutrophils to Candida is not a straightforward consequence of receptor ligation, but is directed by how it is ligated (11–13, 39, 48–52). We have found that upon dual ligation of CR3 by fibronectin and β-glucan, neutrophils demonstrated enhanced chemotaxis, swarming and aggregation, NETosis, and an actively suppressed respiratory burst (Figure 1). Antibody-blocking studies were used to show coincident ligation of CR3 at both the I-domain with the ECM component fibronectin and the lectin-like domain control neutrophil effector functions differently than ligation of either site alone (11–13, 39, 49–52). These studies additionally identified a CR3-mediated regulation of β1 integrins, driving a shift in fibronectin binding from α5β1 to α3β1 (12, 50, 52).
Figure 1. Schematized neutrophil response to C. albicans hyphae in the absence and presence of extracellular matrix. In the absence of ECM (poly-l-lysine, left panel), neutrophils respond to hyphae by chemotaxis, by degranulation and respiratory burst, and by wrapping around fungal filaments in a form of frustrated phagocytosis. In the presence of ECM (Extracellular Matrix, right panel), neutrophils chemotaxis to fungal filaments is faster and more directed, with degranulation and respiratory burst being actively suppressed until the multifocal contact of frustrated phagocytosis. Additionally, in a subset of cells contacting the fungal hyphae, a rapid, respiratory burst independent NETotic response is induced and followed by neutrophil swarming.
In order to be virulent, C. albicans must be capable of transitioning between yeast and hyphal forms (53). The yeast form is readily cleared by neutrophil phagocytosis, the mechanisms of which have been studied extensively. Less work has focused on the neutrophilic response to this filamentous form of the microbe. As Candida destruction necessitates a full-blown response to both forms of the organism, work in our lab has focused on this gap in our understanding of anti-fungal host defense. We found that C. albicans hyphae growing in the kidney of an infected rat induced massive clustering of inflammatory neutrophils that entirely surrounded the hyphae (11). This clustering of human neutrophils could be replicated in vitro with C. albicans hyphae plated on fibronectin but not on hyphae plated in the absence of fibronectin (13). Pretreating hyphae with an anti-β-glucan antibody prevented clustering of neutrophils suggesting that the β-glucan component of the fungal cell wall is important for neutrophil responsiveness (13). Immobilization of purified β-glucan in the presence of fibronectin was a biomimic for Candida hyphae within tissue ECM suggesting that fungal β-glucan is necessary and sufficient for homotypic aggregation (13). Furthermore, this swarming and aggregation took place rapidly, being evident in less than 30 min in vitro (13).
Adding NETosis to the Repertoire of Neutrophil-Mediated Immunity
NETosis was initially described as a pathway of chromatin decondensation and release with requisite NADPH oxidase, elastase, and myeloperoxidase activity in response to activating stimuli (54–56). The initial reports showed relatively slow kinetics, occurring hours following exposure to stimuli, including bacteria, fungi, or PMA (14, 17, 54, 55, 57, 58), though evidence suggests that no de novo gene synthesis is required (59). As additional investigators explored conditions necessary and sufficient to NET release within their experimental systems, some variance in the original paradigm emerged. The "classical" pathway involves entry of the neutrophil into a cell death program that requires ROS and manifests in plasma membrane disruption and NET release 1–4 h after stimulation. This pathway utilized peptidyl arginine deiminase type IV (PAD4) for histone citrullination that leads to chromatin decondensation due to neutralization of histone electrostatic charge normally imparted by arginine but lost upon conversion to citrulline (60). Elastase and myeloperoxidase serve to digest nuclear histones after translocation such that absence of these enzymes impairs NET release (61). A more recently identified early/rapid, or "vital," NET release was identified that can result in extrusion in minutes, independently of ROS and without compromising cell viability, in response to Staphylococcus aureus, C. albicans, and Leishmania promastigotes (13, 62, 63). The "classical" and "vital" NETosis pathways need not be mutually exclusive, as the context of NETotic stimuli presentation, such as timing, viability, size, or morphotype, can drive differential response patterns and kinetics (13, 14, 54, 57, 62–64). ECM ligands in the context of tissue infection can also drive differential neutrophil responses.
Role of Integrins and Extracellular Matrix in the Regulation of NETosis
Our laboratory has demonstrated an integrin-dependent ECM response that both actively suppresses the respiratory burst to Candida hyphae, or immobilized fungal β-glucan, while driving a robust, rapid NETotic response (12, 13). Additionally, work with neonatal neutrophils show that this NETotic anti-fungal pathway is active even though neonatal neutrophils have been shown to be deficient in NETotic responses to other initiating agents, underscoring the importance of stimuli context in evaluating effector function (65, 66).
In addition to our work, evidence to date describes the role of β2 integrins in NET release as it occurs along liver sinusoids or vascular endothelium. Platelet–neutrophil interactions have been shown to occur under conditions of severe sepsis (67) or endotoxemia in which activation of platelet TLR4 promotes platelet binding to neutrophils with ensuing NET release (68). Two recent studies differ with regard to which β2 integrin mediates platelet–neutrophil binding. McDonald et al. (69) show a role for LFA1, although the ligand on the platelet remains to be defined. Rossaint et al. (70) showed that incubation of stimulated platelets with neutrophils ex vivo induced NETosis that could be blocked with anti-CR3 antibodies but not with antibodies against LFA1. Mohanty et al. (71) recently identified that neutrophils form NETs from saliva exposure in a β2 integrin-independent fashion, as LAD1 patients form NETs to saliva and PMA but not to unopsonized S. aureus.
Complement receptor-3 has been shown to regulate apoptosis of neutrophils such that the genetic absence of CR3 delayed the onset of apoptosis of neutrophils after thioglycollate injection (72). Given that CR3 determines a NETotic pathway for Candida, it is of interest to consider whether or not NETotic and apoptotic pathways have common points of regulation. Evidence to date suggests that NETosis and apoptosis both require calcium for initiation but then show divergence in the sense that PAD4 activation does not depend on downstream components of the apoptotic pathway, such as activated caspase, and apoptosis does not depend on PAD4 (73). Indeed, histone citrullination in neutrophils is induced by inflammatory stimuli and not by treatments that induce apoptosis (73). Moreover, treatment of neutrophil-differentiated HL60 cells with calcium ionophore showed that histone citrullination preceded PARP cleavage, such that the decision-making events may be temporal.
The occupancy of one integrin by ligand has been shown to be capable of suppressing the function of other integrins in a phenomenon referred to as trans-dominant inhibition, or integrin crosstalk. For example, activating antibodies specific for the αvβ3 integrin suppress α5β1-dependent phagocytosis and ligation of α4β1 inhibits α5β1-dependent expression of metalloproteinases (74, 75). Ligation of αIIbβ3 induces trans-dominant suppression of target integrins α5β1 and α2β1 (76). Additionally, antibody activation of β1 integrins was shown to increase CR3 adhesion to fibronectin (77) and outside-in activation of β2 integrins via crosslinking was demonstrated to upregulate the expression of β1 integrins (78). These studies suggest that certain integrin-specific ligands provoke integrin crosstalk that could result in alterations in cell migration and invasion. With regard to the anti-Candida response of human neutrophils, we discovered a temporal, interregulatory relationship between the β2 integrin CR3 and regulation of β1 family members and this modulates the response to β-glucan or C. albicans hyphae in the context of ECM (12, 13, 49–52). The extent to which integrin crosstalk operates as a regulatory pathway for other innate immune functions is not well understood.
Neutrophils, Integrins, Extracellular Matrix, NETosis, and Beyond
The host response of neutrophils to C. albicans-infected tissues necessitates ECM contact. Our work and others have clearly demonstrated a regulatory role of ECM in determining neutrophil function, including NETosis. The focus of this review, the role of ECM ligation by neutrophil integrins as it pertains to both host defense functions and the kinetics of these functions, has implications that reach far beyond the anti-fungal response. The totality of ECM involvement in neutrophil host defense in tissues makes accounting for both its presence and the role of integrin engagement an important and under-examined mechanistic aspect of inflammation.
Author Contributions
XO and JR conceived, designed, and wrote the manuscript.
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
This work was supported by the NIH grant GM066194 and HL125265 (JR). Work was also supported by funds from the Department of Surgery, Rhode Island Hospital.
CARD9, caspase recruitment domain-containing protein 9; CR3, complement receptor 3; ECM, extracellular matrix; LAD, leukocyte adhesion deficiency; NETs, neutrophil extracellular traps; PAD4, peptidyl arginine deiminase type IV; PAMP, pathogen-associated molecular pattern; PRR, pattern recognition receptor; ROS, reactive oxygen species.
1. Johnson A. The biology of mating in Candida albicans. Nat Rev Microbiol (2003) 1:106–16. doi: 10.1038/nrmicro752
2. Kullberg BJ, Arendrup MC. Invasive candidiasis. N Engl J Med (2015) 373:1445–56. doi:10.1056/NEJMra1315399
3. Spellberg BJ, Filler SG, Edwards JE. Current treatment strategies for disseminated candidiasis. Clin Infect Dis (2006) 42:244–51. doi:10.1086/499057
4. Wang X, van de Veerdonk FL, Netea MG. Basic genetics and immunology of candida infections. Infect Dis Clin North Am (2016) 30:85–102. doi:10.1016/j.idc.2015.10.010
5. Vincent JL, Anaissie E, Bruining H, Demajo W, el-Ebiary M, Haber J, et al. Epidemiology, diagnosis and treatment of systemic candida infection in surgical patients under intensive care. Intensive Care Med (1998) 24:206–16. doi:10.1007/s001340050552
6. Kourkoumpetis T, Manolakaki D, Velmahos G, Chang Y, Alam HB, De Moya MM, et al. Candida infection and colonization among non-trauma emergency surgery patients. Virulence (2010) 1:359–66. doi:10.4161/viru.1.5.12795
7. Lo H-J, Köhler JR, DiDomenico B, Loebenberg D, Cacciapuoti A, Fink GR. Nonfilamentous C. albicans mutants are avirulent. Cell (1997) 90:939–49. doi:10.1016/S0092-8674(00)80358-X
8. Berman J, Sudbery PE. Candida albicans: a molecular revolution built on lessons from budding yeast. Nat Rev Genet (2002) 3:918–30. doi:10.1038/nrg948
9. Gow NAR, van de Veerdonk FL, Brown AJP, Netea MG. Candida albicans morphogenesis and host defence: discriminating invasion from colonization. Nat Rev Microbiol (2011) 10:112. doi:10.1038/nrmicro2711
10. Winterbourn CC, Kettle AJ. Redox reactions and microbial killing in the neutrophil phagosome. Antioxid Redox Signal (2013) 18:642–60. doi:10.1089/ars.2012.4827
11. Lavigne LM, Albina JE, Reichner JS. Beta-glucan is a fungal determinant for adhesion-dependent human neutrophil functions. J Immunol (2006) 177:8667–75. doi:10.4049/jimmunol.177.12.8667
12. Lavigne LM, O'Brien XM, Kim M, Janowski JW, Albina JE, Reichner JS. Integrin engagement mediates the human polymorphonuclear leukocyte response to a fungal pathogen-associated molecular pattern. J Immunol (2007) 178:7276–82. doi:10.4049/jimmunol.178.11.7276
13. Byrd AS, O'Brien XM, Johnson CM, Lavigne LM, Reichner JS. An extracellular matrix-based mechanism of rapid neutrophil extracellular trap formation in response to Candida albicans. J Immunol (2013) 190:4136–48. doi:10.4049/jimmunol.1202671
14. Branzk N, Lubojemska A, Hardison SE, Wang Q, Gutierrez MG, Brown GD, et al. Neutrophils sense microbe size and selectively release neutrophil extracellular traps in response to large pathogens. Nat Immunol (2014) 15:1017–25. doi:10.1038/ni.2987
15. Leal SM, Vareechon C, Cowden S, Cobb BA, Latgé J-P, Momany M, et al. Fungal antioxidant pathways promote survival against neutrophils during infection. J Clin Invest (2012) 122:2482–98. doi:10.1172/JCI63239
16. Wozniok I, Hornbach A, Schmitt C, Frosch M, Einsele H, Hube B, et al. Induction of ERK-kinase signalling triggers morphotype-specific killing of Candida albicans filaments by human neutrophils. Cell Microbiol (2008) 10:807–20. doi:10.1111/j.1462-5822.2007.01086.x
17. Urban CF, Reichard U, Brinkmann V, Zychlinsky A. Neutrophil extracellular traps capture and kill Candida albicans yeast and hyphal forms. Cell Microbiol (2006) 8:668–76. doi:10.1111/j.1462-5822.2005.00659.x
18. Xia Y, Vetvicka V, Yan J, Hanikýrová M, Mayadas T, Ross GD. The beta-glucan-binding lectin site of mouse CR3 (CD11b/CD18) and its function in generating a primed state of the receptor that mediates cytotoxic activation in response to iC3b-opsonized target cells. J Immunol (1999) 162:2281–90.
19. Phaff H. Cell wall of yeasts. Annu Rev Microbiol (1963) 17:15–30. doi:10.1146/annurev.mi.17.100163.000311
20. Romani L, Montagnoli C, Bozza S, Perruccio K, Spreca A, Allavena P, et al. The exploitation of distinct recognition receptors in dendritic cells determines the full range of host immune relationships with Candida albicans. Int Immunol (2004) 16:149–61. doi:10.1093/intimm/dxh012
21. Ferwerda B, Ferwerda G, Plantinga TS, Willment JA, van Spriel AB, Venselaar H, et al. Human dectin-1 deficiency and mucocutaneous fungal infections. N Engl J Med (2009) 361:1760–7. doi:10.1056/NEJMoa0901053
22. Lowman DW, Greene RR, Bearden DW, Kruppa MD, Pottier M, Monteiro MA, et al. Novel structural features in Candida albicans hyphal glucan provide a basis for differential innate immune recognition of hyphae versus yeast. J Biol Chem (2014) 289:3432–43. doi:10.1074/jbc.M113.529131
23. Glocker E-O, Hennigs A, Nabavi M, Schäffer AA, Woellner C, Salzer U, et al. A homozygous CARD9 mutation in a family with susceptibility to fungal infections. N Engl J Med (2009) 361:1727–35. doi:10.1056/NEJMoa0810719
24. van Bruggen R, Drewniak A, Jansen M, van Houdt M, Roos D, Chapel H, et al. Complement receptor 3, not Dectin-1, is the major receptor on human neutrophils for beta-glucan-bearing particles. Mol Immunol (2009) 47:575–81. doi:10.1016/j.molimm.2009.09.018
25. Brown GD. Dectin-1: a signalling non-TLR pattern-recognition receptor. Nat Rev Immunol (2006) 6:33–43. doi:10.1038/nri1745
26. Wright SD, Silverstein SC. Receptors for C3b and C3bi promote phagocytosis but not the release of toxic oxygen from human phagocytes. J Exp Med (1983) 158:2016–23. doi:10.1084/jem.158.6.2016
27. Li X, Utomo A, Cullere X, Choi MM, Milner DA, Venkatesh D, et al. The β-glucan receptor dectin-1 activates the integrin Mac-1 in neutrophils via Vav protein signaling to promote Candida albicans clearance. Cell Host Microbe (2011) 10:603–15. doi:10.1016/j.chom.2011.10.009
28. Gantner BN, Simmons RM, Underhill DM. Dectin-1 mediates macrophage recognition of Candida albicans yeast but not filaments. EMBO J (2005) 24:1277–86. doi:10.1038/sj.emboj.7600594
29. Forsyth CB, Mathews HL. Lymphocyte adhesion to Candida albicans. Infect Immun (2002) 70:517–27. doi:10.1128/IAI.70.2.517-527.2002
30. Hynes RO. Integrins: bidirectional, allosteric signaling machines. Cell (2002) 110:673–87. doi:10.1016/S0092-8674(02)00971-6
31. Hynes RO. Integrins: versatility, modulation, and signaling in cell adhesion. Cell (1992) 69:11–25. doi:10.1016/0092-8674(92)90115-S
32. Bauer TR, Hickstein DD. Gene therapy for leukocyte adhesion deficiency. Curr Opin Mol Ther (2000) 2:383–8.
33. Yung RL, Ray D, Mo RR, Chen JT. Cell integrin overexpression as a model of murine autoimmunity. Biol Proced Online (2003) 5:211–21. doi:10.1251/bpo64
34. Yakubenko VP, Lishko VK, Lam SC-T, Ugarova TP. A molecular basis for integrin alphaMbeta 2 ligand binding promiscuity. J Biol Chem (2002) 277:48635–42. doi:10.1074/jbc.M208877200
35. Diamond MS, Garcia-Aguilar J, Bickford JK, Corbi AL, Springer TA. The I domain is a major recognition site on the leukocyte integrin Mac-1 (CD11b/CD18) for four distinct adhesion ligands. J Cell Biol (1993) 120:1031–43. doi:10.1083/jcb.120.4.1031
36. Kim M, Carman CV, Yang W, Salas A, Springer TA. The primacy of affinity over clustering in regulation of adhesiveness of the integrin alphaL, beta2. J Cell Biol (2004) 167:1241. doi:10.1083/jcb.200404160
37. Xia Y, Ross GD. Generation of recombinant fragments of CD11b expressing the functional beta-glucan-binding lectin site of CR3 (CD11b/CD18). J Immunol (1999) 162:7285–93.
38. Ross GD. Regulation of the adhesion versus cytotoxic functions of the Mac-1/CR3/alphaMbeta2-integrin glycoprotein. Crit Rev Immunol (2000) 20:197–222. doi:10.1615/CritRevImmunol.v20.i3.20
39. O'Brien XM, Heflin KE, Lavigne LM, Yu K, Kim M, Salomon AR, et al. Lectin site ligation of CR3 induces conformational changes and signaling. J Biol Chem (2012) 287:3337–48. doi:10.1074/jbc.M111.298307
40. Vetvicka V, Thornton BP, Ross GD. Soluble beta-glucan polysaccharide binding to the lectin site of neutrophil or natural killer cell complement receptor type 3 (CD11b/CD18) generates a primed state of the receptor capable of mediating cytotoxicity of iC3b-opsonized target cells. J Clin Invest (1996) 98:50–61. doi:10.1172/JCI118777
41. Vĕtvicka V, Hanikýrová M, Vĕtvicková J, Ross GD. Regulation of CR3 (CD11b/CD18)-dependent natural killer (NK) cell cytotoxicity by tumour target cell MHC class I molecules. Clin Exp Immunol (1999) 115:229–35. doi:10.1046/j.1365-2249.1999.00800.x
42. Vetvicka V, Thornton BP, Wieman TJ, Ross GD. Targeting of natural killer cells to mammary carcinoma via naturally occurring tumor cell-bound iC3b and beta-glucan-primed CR3 (CD11b/CD18). J Immunol (1997) 159:599–605.
43. Hong F, Hansen RD, Yan J, Allendorf DJ, Baran JT, Ostroff GR, et al. Beta-glucan functions as an adjuvant for monoclonal antibody immunotherapy by recruiting tumoricidal granulocytes as killer cells. Cancer Res (2003) 63:9023–31.
44. Hong F, Yan J, Baran JT, Allendorf DJ, Hansen RD, Ostroff GR, et al. Mechanism by which orally administered beta-1,3-glucans enhance the tumoricidal activity of antitumor monoclonal antibodies in murine tumor models. J Immunol (2004) 173:797–806. doi:10.4049/jimmunol.173.2.797
45. Li B, Allendorf DJ, Hansen R, Marroquin J, Ding C, Cramer DE, et al. Yeast beta-glucan amplifies phagocyte killing of iC3b-opsonized tumor cells via complement receptor 3-Syk-phosphatidylinositol 3-kinase pathway. J Immunol (2006) 177:1661–9. doi:10.4049/jimmunol.177.3.1661
46. Nathan C, Srimal S, Farber C, Sanchez E, Kabbash L, Asch A, et al. Cytokine-induced respiratory burst of human neutrophils: dependence on extracellular matrix proteins and CD11/CD18 integrins. J Cell Biol (1989) 109:1341–9. doi:10.1083/jcb.109.3.1341
47. Nathan CF. Neutrophil activation on biological surfaces. Massive secretion of hydrogen peroxide in response to products of macrophages and lymphocytes. J Clin Invest (1987) 80:1550–60. doi:10.1172/JCI113241
48. Fox ED, Heffernan DS, Cioffi WG, Reichner JS. Neutrophils from critically ill septic patients mediate profound loss of endothelial barrier integrity. Crit Care (2013) 17:R226. doi:10.1186/cc13049
49. Harler MB, Reichner J. Increased neutrophil motility by beta-glucan in the absence of chemoattractant. Shock (2001) 16:419–24. doi:10.1097/00024382-200116060-00003
50. Harler MB, Wakshull E, Filardo EJ, Albina JE, Reichner JS. Promotion of neutrophil chemotaxis through differential regulation of beta 1 and beta 2 integrins. J Immunol (1999) 162:6792–9.
51. Tsikitis VL, Albina JE, Reichner JS. Beta-glucan affects leukocyte navigation in a complex chemotactic gradient. Surgery (2004) 136:384–9. doi:10.1016/j.surg.2004.05.014
52. Tsikitis V, Morin NA, Harrington EO, Ablina JE, Reichner JS. The lectin-like domain of complement receptor 3 protects endothelial barrier function from activated neutrophils. J Immunol (2004) 173:1284–91. doi:10.4049/jimmunol.173.2.1284
53. Whiteway M, Oberholzer U. Candida morphogenesis and host-pathogen interactions. Curr Opin Microbiol (2004) 7:350–7. doi:10.1016/j.mib.2004.06.005
54. Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, et al. Neutrophil extracellular traps kill bacteria. Science (2004) 303:1532–5. doi:10.1126/science.1092385
55. Fuchs TA, Abed U, Goosmann C, Hurwitz R, Schulze I, Wahn V, et al. Novel cell death program leads to neutrophil extracellular traps. J Cell Biol (2007) 176:231–41. doi:10.1083/jcb.200606027
56. Steinberg BE, Grinstein S. Unconventional roles of the NADPH oxidase: signaling, ion homeostasis, and cell death. Sci STKE (2007) 2007:e11. doi:10.1126/stke.3792007pe11
57. Urban CF, Ermert D, Schmid M, Abu-Abed U, Goosmann C, Nacken W, et al. Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans. PLoS Pathog (2009) 5:e1000639. doi:10.1371/journal.ppat.1000639
58. Bruns S, Kniemeyer O, Hasenberg M, Aimanianda V, Nietzsche S, Thywissen A, et al. Production of extracellular traps against Aspergillus fumigatus in vitro and in infected lung tissue is dependent on invading neutrophils and influenced by hydrophobin RodA. PLoS Pathog (2010) 6:e1000873. doi:10.1371/journal.ppat.1000873
59. Sollberger G, Amulic B, Zychlinsky A, Amulic B, Cazalet C, Hayes GL, et al. Neutrophil extracellular trap formation is independent of de novo gene expression. PLoS One (2016) 11:e0157454. doi:10.1371/journal.pone.0157454
60. Wang Y, Li M, Stadler S, Correll S, Li P, Wang D, et al. Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation. J Cell Biol (2009) 184:205–13. doi:10.1083/jcb.200806072
61. Papayannopoulos V, Metzler KD, Hakkim A, Zychlinsky A. Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps. J Cell Biol (2010) 191:677–91. doi:10.1083/jcb.201006052
62. Pilsczek FH, Salina D, Poon KKH, Fahey C, Yipp BG, Sibley CD, et al. A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus. J Immunol (2010) 185:7413–25. doi:10.4049/jimmunol.1000675
63. Rochael NC, Guimarães-Costa AB, Nascimento MTC, DeSouza-Vieira TS, Oliveira MP, Garcia e Souza LF, et al. Classical ROS-dependent and early/rapid ROS-independent release of neutrophil extracellular traps triggered by Leishmania parasites. Sci Rep (2015) 5:18302. doi:10.1038/srep18302
64. Kenno S, Perito S, Mosci P, Vecchiarelli A, Monari C. Autophagy and reactive oxygen species are involved in neutrophil extracellular traps release induced by C. albicans Morphotypes. Front Microbiol (2016) 7:879. doi:10.3389/fmicb.2016.00879
65. Byrd AS, O'Brien XM, Laforce-Nesbitt SS, Parisi VE, Hirakawa MP, Bliss JM, et al. NETosis in neonates: evidence of a reactive oxygen species-independent pathway in response to fungal challenge. J Infect Dis (2016) 213:634–9. doi:10.1093/infdis/jiv435
66. Yost CC, Cody MJ, Harris ES, Thornton NL, McInturff AM, Martinez ML, et al. Impaired neutrophil extracellular trap (NET) formation: a novel innate immune deficiency of human neonates. Blood (2009) 113:6419–27. doi:10.1182/blood-2008-07-171629
67. Clark SR, Ma AC, Tavener SA, McDonald B, Goodarzi Z, Kelly MM, et al. Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat Med (2007) 13:463–9. doi:10.1038/nm1565
68. Caudrillier A, Kessenbrock K, Gilliss BM, Nguyen JX, Marques MB, Monestier M, et al. Platelets induce neutrophil extracellular traps in transfusion-related acute lung injury. J Clin Invest (2012) 122:2661–71. doi:10.1172/JCI61303
69. McDonald B, Urrutia R, Yipp BG, Jenne CN, Kubes P. Intravascular neutrophil extracellular traps capture bacteria from the bloodstream during sepsis. Cell Host Microbe (2012) 12:324–33. doi:10.1016/j.chom.2012.06.011
70. Rossaint J, Herter JM, Van Aken H, Napirei M, Döring Y, Weber C, et al. Synchronized integrin engagement and chemokine activation is crucial in neutrophil extracellular trap-mediated sterile inflammation. Blood (2014) 123:2573–84. doi:10.1182/blood-2013-07-516484
71. Mohanty T, Sjögren J, Kahn F, Abu-Humaidan AHA, Fisker N, Assing K, et al. A novel mechanism for NETosis provides antimicrobial defense at the oral mucosa. Blood (2015) 126:2128–37. doi:10.1182/blood-2015-04-641142
72. Coxon A, Rieu P, Barkalow FJ, Askari S, Sharpe AH, von Andrian UH, et al. A novel role for the beta 2 integrin CD11b/CD18 in neutrophil apoptosis: a homeostatic mechanism in inflammation. Immunity (1996) 5:653–66. doi:10.1016/S1074-7613(00)80278-2
73. Neeli I, Khan SN, Radic M. Histone deimination as a response to inflammatory stimuli in neutrophils. J Immunol (2008) 180:1895–902. doi:10.4049/jimmunol.180.3.1895
74. Huhtala P, Humphries MJ, McCarthy JB, Tremble PM, Werb Z, Damsky CH. Cooperative signaling by alpha 5 beta 1 and alpha 4 beta 1 integrins regulates metalloproteinase gene expression in fibroblasts adhering to fibronectin. J Cell Biol (1995) 129:867–79. doi:10.1083/jcb.129.3.867
75. Blystone SD, Graham IL, Lindberg FP, Brown EJ. Integrin alpha v beta 3 differentially regulates adhesive and phagocytic functions of the fibronectin receptor alpha 5 beta 1. J Cell Biol (1994) 127:1129–37. doi:10.1083/jcb.127.4.1129
76. Díaz-González F, Forsyth J, Steiner B, Ginsberg MH. Trans-dominant inhibition of integrin function. Mol Biol Cell (1996) 7:1939–51. doi:10.1091/mbc.7.12.1939
77. van den Berg JM, Mul FP, Schippers E, Weening JJ, Roos D, Kuijpers TW. Beta1 integrin activation on human neutrophils promotes beta2 integrin-mediated adhesion to fibronectin. Eur J Immunol (2001) 31:276–84. doi:10.1002/1521-4141(200101)31:1<276:AID-IMMU276>3.0.CO;2-D
78. Werr J, Eriksson EE, Hedqvist P, Lindbom L. Engagement of beta2 integrins induces surface expression of beta1 integrin receptors in human neutrophils. J Leukoc Biol (2000) 68:553–60.
Keywords: NETs, extracellular matrix, neutrophils, integrins, Candida
Citation: O'Brien XM and Reichner JS (2016) Neutrophil Integrins and Matrix Ligands and NET Release. Front. Immunol. 7:363. doi: 10.3389/fimmu.2016.00363
Received: 29 July 2016; Accepted: 02 September 2016;
Published: 19 September 2016
Edited by:Mariana Julieta Kaplan, National Institute of Arthritis and Musculoskeletal and Skin Diseases, USA
Reviewed by:Ian Dransfield, University of Edinburgh, UK
Yan-Qing Ma, Blood Center of Wisconsin, USA
Copyright: © 2016 O'Brien and Reichner. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Jonathan S. Reichner, email@example.com


text:
Updates on happenings with Covenant Advent Church
It does not lessen the value of an individual to receive someone else's advice or to request advice or opinion from someone else. Hearing a different point of view does not diminish anyone...
Categories: Daily Devotional
Tags: daily devotionals, life's lessons, loving person makes for best home, covenant relationship with God, happily married, God in the home, christian home, in loving service needs of others, church without spot or wrinkle, marital bliss maintain restore, respect love dignity in a marriage, : training up a child
As we look at the past history of God's church, we can acknowledge that like Eve, God's bride has many a time gone astray. Jesus still love her and did sacrifice His life for her, for the purpose of winning her back so He can...
Watch live our weekly worship services
Saturday: 11/30/19
Speaker: Crageton Green
10:00 am Sabbath School
11:30 am Divine Service
3:30 pm Bible Study
Various Channels you can watch our live stream and archived programs:


text:
A new study carried out by a research team at The University of Western Australia and Fertility Specialists of Western Australia has found that women undergoing IVF who have had embryos fail to implant have more success using frozen ones than fresh ones.
Internationally renowned breast cancer surgeon Professor Christobel Saunders from The University of Western Australia is one of 14 women who have been inducted into the WA Women's Hall of Fame today.
The potential for devastating crop diseases to be controlled biologically is one step closer after a discovery by researchers from The University of Western Australia and Huazhong Agricultural University in China.
Plant scientists at The University of Western Australia have discovered a completely new family of small proteins called PLPs (PawL Peptides) that form by piggybacking on other proteins.
New research led by a scholar from The University of Western Australia has found that the majority of midwives support vaccinations for babies and children.
The Faculty of Engineering and Mathematical Sciences' (EMS) Campus Services Manager, Paul McCann recently visited the Winter Palace of Sport, in Sofia, Bulgaria this month. His role as Australian Team Leader includes supervision of all team staff and logistics, as well as a Championship official role, the Australian Delegate to the International Ice Hockey Federation (IIHF) Tournament Directorate.
Fish catches by Thailand's distant-water fleet fishing throughout the Indo-Pacific are almost seven times higher than the numbers reported to the United Nations, according to new research carried out by The University of Western Australia and The University of British Columbia.
Researchers at The University of Western Australia are part of an international team that has discovered why some plant species are more successful than others at successfully invading new regions.
An Australian scientist has created the most detailed map ever of clouds of high-velocity gas in the Universe around us.
An internationally acclaimed mathematician, UWA Emeritus Professor Cheryl Praeger, has been awarded an honorary doctorate from The University of Queensland (UQ), in recognition of her distinguished service to mathematics, her distinguished career achievement and academic distinction.
CRICOS Code: 00126G


text:
New design on the KTH website
From January 2019, the appearance of KTH's website will be updated.
During 2018, a revised graphic profile has been introduced at KTH with a review of colors, fonts and graphical elements. The updated visual identity takes a holistic approach to KTH's communication channels. The purpose is to create a single visual impact that apply to digital as well as print-based material.
The update of the graphical profile also means the introduction of a new design on the KTH website. These are the most significant changes in this revision:
- The KTH web site takes a larger width in desktop view, i e on a regular computer screen
- Body text on standard pages is set in a serif font
- A number of colors are deleted from the web color palette
- The site gets increased responsiveness, which means it will perform better at different screen widths, from computer screens to mobile phones
The style changes will not be introduced simultaneously in all parts of the KTH website. It will successively be applied to the various web applications. First, the new look will apply to content in the Polopoly system. The new design is implemented on Polopoly based content from January, 2019.
Does the new design affect me?
As a web editor in Polopoly, there are a number of things you need to consider.
The increased side width gives wider columns, which means wider slots for images. This may require manual adjustments to the images.
Some block templates are affected by the new form. Appearance settings that can be made in these blocks are changed or deleted completely, which has consequences for how the content is presented on the site.
Because of this you should review the following pages and assess how the changes affect the part of the site you are maintaining. Some are things you can act on right now, like the ones that concern image sizes. Other things are easier to approach when the new design is in place, such as the outcome of teaser settings that disappears.
- KTH start page . An example of how the KTH home page looks in the new design.
- Standard page . An example of a common standard page.
- Page and column widths . The width ratios that apply to different page types and columns.
- Image widths . This is what you need to consider when it comes to images.
- Appearance types that expire . Some appearance settings are transitioned to other standardized variants.
- Blocks that are affected . Some blocks appear otherwise in the new design.
- Checklist . Summary of what you as a web editor need to think about.
What if I don't do anything?
No content disappears with the new design. Your web pages will not be "broken". But the content will be presented in a new text format, with fewer colors and with other space ratios. In some cases this means that pages left untouched will not look as optimized for the new style as they could have been.
This applies mainly to pages with column splits and a lot of teaser blocks, such as start pages. Advanced page structures that gather many different types of content are more sensitive to design changes than easily-structured pages with straightforward disposition of text, images, links and c.
The polopoly system will work as usual. However, some appearance settings in the templates are deleted and converted into other options.
Do you have questions about the new design or have thoughts on how it will affect your content? Contact firstname.lastname@example.com .


text:
Milwaukee Youth Theatre
Performing Arts Weekly: Oct. 19-25, 2017
Sex with Strangers? Reformation-era music? A cat's personal biography? All that and more on Milwaukee stages this week! Read more
Intros and Outros at Milwaukee Youth Theatre
Off the Cuff sits down with Artistic Director Therese Burazin of Milwaukee Youth Theatre as she prepares to pass the torch to Associate Director Brandon Herr in the company's 25th season. Read more
Auditions For Mr. Popper's Penguins
Milwaukee Youth Theatre will be producing a stage adaptation of the classic children's book Mr. Popper's Penguins. The 1938 story of a professional house painter who is forced to adopt a rather large group of penguins has been a favorite for .. Read more
Number the Stars Auditions
Lois Lowry's 1989 historical fiction book Number the Stars is one of the top-selling children's books of all time in the US. More than that, it's an important story of the life and struggle of the oppressed during World War II. It concerns a ten.. Read more
Milwaukee Youth Theatre Stages 'Stuart Little'
E.B. White was on a train when he dreamed of the story of a boy that behaved like a mouse. He prodded the dreams a little bit and they became stories he would tell to his nieces and nephews. He typed-up the stories of a mouse with human parents an.. Read more
Milwaukee Youth Theatre presents A Midsummer Night's Dream
The story of four young lovers becomes the story of four really young lovers as Milwaukee Youth Theatre present A Midsummer Night's Dream next month. Staged just in time for the days leading-in to Valentine's Day, the youth theatre company will be.. Read more
Little Mermaid Auditions for Milwaukee Youth Theatre
MilwaukeeYouth Theatre has announced fourshows for its coming 2014-2015 season. This month they're looking to cast forthe first show of the season: Disney's The Little Mermaid, JR. Directedand choreographed by Dan Tellez, the show will run Oct.. Read more
Shepherd Express Endorsements
If you were to describe the ideal candidate for Milwaukee County sheriff, you couldn't do much better than Milwaukee Police Lt. Chris Moews. He thoroughly understands the issues and problems facing Milwaukee County, and actually has realist... Read more
Eat Pray Love
For many of us, Manhattan's tree-lined side streets offer a romantic ideal of urban life, but for the protagonist of Eat Pray Love, familiarity breeds banality. The change of scene demanded by Liz (Julia Roberts) is triggered by the realiza... Read more
Finding a Loophole
For years, conservatives denounced the idea of criminals avoiding punishment for their heinous misdeeds by "finding a loophole" and "getting off on a technicality."The right wing always made it sound as if our legal system had be Read more
Mummies: Secrets of the Pharaohs
Researching Egyptian pharaohs is genuinely dangerous work that takes archaeologists to unforgiving desert climates and treacherous tombs, and pits them against thieves who want to get their own hands on historical treasures for Read more
Legally Blonde: The Musical
Adapted from the 2001 hit Reese Witherspoon comedy, Legally Blonde the Musical debuted on Broadway in 2007, telling the story of sorority girl Elle Woods. On her quest to win back her boyfriend, Warner, Elle leaves a world of... Read more


text:
Azerbaijan and Tajikistan are considering joining the Islamic military coalition led by Saudi Arabia.
The due information was published in the "Al-Sharq al-Awsat" newspaper, Oxu.Az reports citing ITAR-TASS.
The Tajik authorities are currently considering a proposal by Saudi Arabia to enter into a coalition to combat Islamic terrorism.
The Ambassador Sharifi Azamsho Latifzody said that Tajik President Emomali Rakhmon will visit the Middle East country and meet with King Salman in January.
The sides will discuss issues of strengthening cooperation in the fight against terrorism, in particular, the opportunity to participate in Dushanbe Muslim Military Unit.
The head of Azerbaijan's diplomatic mission in the Kingdom Rasim Rzayev confirmed that Baku is also considering a proposal received from Saudi Arabia.
"Azerbaijan supports the desire of the kingdom in the fight against terrorism in all its manifestations, it is in the interests of our country. Therefore, we are studying a proposal to enter into the Islamic military coalition," the diplomat said.
On December 15, Saudi Arabia announced the establishment of an Islamic coalition to fight terrorism militarily and ideologically.
In addition to the kingdom, another 33 countries joined coalition: Egypt, Jordan, United Arab Emirates, Pakistan, Bahrain, Bangladesh, Benin, Turkey, Tunisia, Senegal, Sierra Leone, Sudan, Somalia, Palestine, Qatar, Kuwait, Lebanon , Libya, Mali, Malaysia, Niger, Nigeria, Yemen, Chad, Togo, Gabon, Djibouti, Guinea, Morocco, Cote d'Ivoire, Mauritania, Maldives and Comoros.
More than 10 Islamic countries, including Indonesia, supported the establishment of the coalition.


text:
Established in 1831 to "tend to the regeneration of the Drama", the Garrick Club is now the scene of an increasingly heated drama over women.
The "gentlemen only" club in Covent Garden favoured by actors has sent a letter to its members, including Sir Roger Moore and Stephen Fry, informing them that it has abandoned its ban on women guests from sitting at the hallowed centre table of its Coffee Room.
For the first time, women will also now be allowed to visit the cocktail bar before 9 o'clock in the evening and venture "under the stairs".
Jonathan Acton Davis QC, the Garrick's chairman, says the Equality Act, introduced by the former Labour minister Harriet Harman, means that "each of those prohibitions was discriminatory and would be illegal". The act denotes that "all guests must receive the same treatment irrespective of gender", he adds.
"The decision in relation to the centre table was the most difficult. The long traditions of the club are strongly in favour of restricting use of the centre table to men."
On the day the act became law this month, Lady Antonia Fraser, the historian, sat down, defiantly, at the centre table. Now, a fightback has begun, with members calling for a special general meeting to debate a resolution that "cherishes the traditional role of the centre table".
Acton Davis warns members to withdraw the motion or such a meeting "may be damaging to the club because it will inevitably lead to publicity which is unlikely to portray us favourably".


text: Request Information Thank you for your interest in Ovient's training programs. Please use the form below to tell us more about your needs or to request a free consultation. You can also give us a call at 408-524-1649. Your First Name (required) Your Last Name (required) Your Company (required) Your Title Your Email (required) Your Phone Number Which training program are you interested in? (required) Communication Awesomeness CoachingSilicon Valley Business English CoachingTeam TrainingOther Who is the training for? (required) Just me!Others at my company How many people need training? ---12-56-1011-2526-5051-100101 or more Do you have any other questions? Please add me to your email list.


text: Getting rid of grandpa's estate, this young guy was selling 4 bikes on craigslist that have been sitting in an attic for years!!! This '59 Schwinn was in the mix so I popped! Here it is now. It is one more bike on the road with new rubber and 52 prior years of existence and many more down the road. :wink: Total investment: $23.15 Link to build thread: viewtopic.php?f=55&t=42286&st=0&sk=t&sd=a


text:
Civil Eyewear focuses on ways to provide eyeglasses of every kind. We are constantly adding and improving on new types of eyewear. Paying an outrageous amount for glasses or sunglasses is not something people should HAVE to do. Larger enterprises that could be providing you magnitudes of a better price opt to inflate their profits instead.
CIVIL has and will always continue to streamline the industry to give fair prices without compromised quality. We will always be progressively providing an alternative for the smart consumer just like Superior Essay Writing Service.


text:
The staff of LICADD recognizes World AIDS Day as an important reminder of the need for health education and the use of harm-reduction counseling. As health care professionals who often talk to individuals just beginning to address their substance use, other health issues are always a part of the conversations we have. And it's a conversation people are often scared to have, an issue we fear to address – of the 1.1 million people living with HIV in the U.S., only 1 in 7 are aware of the infection.
It's not an easy thing to open up about – our staff know how challenging working through stigma and fear can be. Sadly, there's still a lot of stigma around HIV despite advances in treatment and prevention options like Pre-Exposure Prophylaxis (PrEP) and Post-Exposure Prophylaxis (PEP).
If there's a skill these clinicians have above all else, it's the ability to sit with nervous people and help them find what they need: a sense of calm, a plan to get well, and the motivation to act. It's a cliché to say there's no judgment in therapy, but it's true, and you feel it in these offices. We're proud to help our clients connect not just to OASAS treatment, but to needed medical care for HIV/AIDS and any other needs as well.


text:
Holiday Happenings at the Forum – Your Local Gift Guide
The Forum has a gift for everyone! Here are the events + notable deals happening this Holiday Season.
Events –
Meadowlark –
Meadowlark is having a Holiday Open House!
Saturday, December 8 from 1 – 4pm
Local Gift Guide + Promotions
Ki Spa Candles –
Ki Spa's Holiday Top Seller is BACK! This intoxicating Roland Pine candle has beautiful notes of Siberian Fir, Cilantro and Citrus to uplift the spirit, while filling your room with the fresh cut scent of pine boughs. The Candle is pure soy wax, clean burning and has amazing 75-hour burn time!
Beauty Bar Boutique –
New all-natural Sugaring Wax hair removal available now!
Tama Cafe –
Tama has the perfect gift for any occasion this season! Get a sampler of Tama's most popular teas in a 3-tin set!
Now in-store for only $23.95!
Tama is now offering catering services for small and large events!
Included items: sandwiches, sides, deserts and wide range of beverage options.
*Vegan + vegetarian options available
Spectrum Fine Jewelry –
Owner, Star Sosa is retiring after 20 successful years! Spectrum will be closing and having sales up to 70% off select items!
Diamond studs only $29.99 from December 6 to December 8! Three-days only!!
City Mac –
20%-off accessories *excludes Apple products
KBueno –
Gift cards available + hoodies & t-shirts!
True Blue Butcher and Table –
Gift cards available!


text:
Moet & Chandon Rose Imperial Champagne NV 750ml
Sold out
Moet Rose Champagne, This is the drink for that special person in your life, Moet Rosé is perfect for celebrations, or to simply enjoy chilled on a warm summers day. A winner with the ladies.
Alcohol Volume - 12% | Region - France
Size: 750ml
Hellodrinks are proud to deliver your Moet Rose Champagne to your door across Australia.


text: This home has been completely renovated from top to bottom. Upgraded kitchen with all new cabinetry, granite counters, and stainless steel appliances. The main floor also features gleaming hardwood floors, 10 ft ceilings, an open modern design that includes a dining room as well as a separate family room. Upstairs you will find an oversized master bedroom with private deck and walk-in closet. The 2nd floor also includes two other good size bedrooms, laundry, and an open area perfect for kids or an office. Both washrooms have been completely renovated. Other upgrades include 200 amp service, hi eff furnace, low E windows, (except stainless window), new exterior front door, shingles (approx 7 yrs). Private fully fenced back yard with large deck. Private 2 car driveway. Come and view this wonderful home today.


text:
The 4th night of the refuges - Refuge du Blancrupt
Phone CallEmailOfficial website
344Lac BlancSituer
Lac Blanc 1200
68370OrbeyRefuge Étang du Devin
At the Refuge du Blancrupt, enjoy the experience of tree climbing at Lac Blanc and spend a convivial evening around various board games. With family or friends, play your favorite games and discover new ones. Enjoy this fun weekend in the heart of the Regional Natural Park of Ballons des Vosges.
Useful Information
- Organised by
- Terre d'Est
- Opening hours
- Saturday 15h > Sunday 12h.
- Length of visit/event
- Half-day
- Prices (events, products, etc.)
- Adults : 43€ / -10 yo : 31€
- Booking necessary
- Parking gratuit pour voitures
- SatNav Coordinates
- 7.0939117000000448.1340487


text:
Easter 2017 - The First Easter
April 16, 2017 Pastor: Ryan Rice
Scripture: Luke 24:1–24:12
- Listen
- Downloads
"I am the resurrection and the life. The one who believes in me with live, even though they die." John 11:25
Jesus Christ claimed to not just know the way of salvation, but to be the way of salvation. These teachings led Him to the cross. He is one of the most loved and hated people in the world. The disciples were a band of misfits whom Jesus mentored. Just days earlier they had their leader and teacher crucified. They believed in him, but amid this tragedy they struggled to understand the empty tomb. Did someone steal the body? Could he have been buried alive? Could it be possible that Jesus actually rose from the dead?
Crucifixion was perhaps the most heinous death imaginable and Jesus delivered himself willing to it. He served as a sacrifice for our sins so that He might rise in triumph over death. Jesus brought forgiveness when He took our sins on the cross. He became a substitute for us by taking on the sins of the world.
God sent His angels to bring the news of the resurrection. They reminded the women who came to tend Jesus body that He told them He would be crucified and rise again. They brought this message back to the disciples. They finally understand the culmination of Jesus teachings and promises.
"For by grace you have been saved through faith. And this is not your own doing; it is the gift of God, not a result of works, so that no one may boast." Ephesians 2:8-9
If you were to die today would you be certain you would go to heaven? You can have this assurance that if you place your faith in Him, you will be saved.