text:
City Hall (38 Viewing)
Important messages from the administrators and developers654 Threads8,431 Posts
Release Updates for September...
Today, 17:47 by lokiare
The Tavern (143 Viewing)
General discussion about Fantasy Grounds9,356 Threads85,028 Posts
Blood Dice announced as part...
Today, 16:46 by ddavison
The Commons (56 Viewing)
Non-Fantasy Grounds related discussion about gaming.1,441 Threads13,111 Posts
September 26th, 2023, 21:15 by Gawain the Great
The House of Healing - Fantasy Grounds (80 Viewing)
Customer support
The place to find help for technical problems running Fantasy Grounds6,442 Threads48,413 Posts
SWADE Error for GM & Players...
Today, 16:39 by Moon Wizard
The House of Healing - Forge (16 Viewing)
Customer support
The place to find help for technical problems running Fantasy Grounds Forge127 Threads1,423 Posts
September 10th, 2023, 13:04 by Talon 46
The Laboratory (56 Viewing)
A place to discuss and report problems with the latest public test version.790 Threads11,144 Posts
Today, 17:00 by Moon Wizard
Fantasy Grounds Game Days (24 Viewing)
Official Free Fantasy Grounds Game Days82 Threads97 Posts
September 25th, 2023, 16:16 by GregRex
Conventions (141 Viewing)
FG Con starts Friday, April 16th and runs through Sunday April 18th, 2021
Sub-Forums:320 Threads5,133 Posts
August 27th, 2023, 23:46 by GregRex
D&D Adventurer's League Games (56 Viewing)
General info on what you need to schedule, participate or host Adventurer League games for D&D.563 Threads3,592 Posts
Seats Available for June 24th...
June 24th, 2023, 03:16 by viviolay
LFG - Looking for Group (196 Viewing)
A board for finding games, announcing campaigns and scheduling play times. Please link games to the Game Calendar for Recruiting.
Sub-Forums:16,086 Threads106,882 Posts
Today, 16:25 by AFNick12
Pathfinder Society Games (58 Viewing)
General Info and Recruiting for playing Pathfinder Organized Play913 Threads23,273 Posts
*** Game Announcement thread...
September 13th, 2023, 06:53 by stephan_
Starfinder Society Games (37 Viewing)
General Info and Recruiting for playing Starfinder Organized Play250 Threads2,903 Posts
Starfinder Society Scenario...
Today, 01:41 by Killakia
Barbarians of Lemuria (26 Viewing)
Barbarians of Lemuria Forum5 Threads107 Posts
Honor and Intrigue Feedback...
September 2nd, 2023, 21:41 by Moon Wizard
Call of Cthulhu (100 Viewing)
Discuss the Call of Cthulhu ruleset, adventure modules, schedule games or anything else related to this.
Sub-Forums:640 Threads5,721 Posts
Best introduction adventure...
Today, 17:37 by OB1Sean
Castles & Crusades (54 Viewing)
Discuss the Castles & Crusades ruleset, adventure modules, schedule games or anything else related to this.393 Threads3,965 Posts
September 18th, 2023, 13:52 by Hapa
Cyberpunk RED (10 Viewing)
Discuss the Cyberpunk RED ruleset, adventure modules, schedule games or anything else related to this.22 Threads181 Posts
Official Release! And What's...
Yesterday, 04:27 by Nightstride
Dune 2d20 (23 Viewing)8 Threads113 Posts
Official Dune 2d20 Bug Report...
September 6th, 2023, 18:24 by superteddy57
Dungeons & Dragons (647 Viewing)
All editions of Dungeons & Dragons
Sub-Forums:7,684 Threads83,497 Posts
Yesterday, 09:04 by Zacchaeus
Fallout RPG (28 Viewing)
In 2077, the storm of nuclear war reduced most of the planet to cinders. From the ashes of nuclear devastation, a new civilization will struggle to arise. A civilization you will shape.78 Threads632 Posts
Any quality maps for fallout...
September 24th, 2023, 22:48 by Draykor
Pathfinder Roleplaying Games (95 Viewing)
Both 1st edition and 2nd edition
Sub-Forums:1,928 Threads24,239 Posts
Today, 17:10 by Blahness98
Savage Worlds (54 Viewing)
Discuss the Savage World ruleset, adventure modules, schedule games or anything else related to this.2,427 Threads21,704 Posts
Today, 14:22 by Lonewolf
Star Trek Adventures 2d20 (32 Viewing)
Another 2d20 game by Modiphius. Ruleset by SmiteWorks.20 Threads320 Posts
Official Star Trek 2d20 Bug...
Today, 15:47 by Caratacus
Starfinder (21 Viewing)
Science Fantasy by the makers of Pathfinder.679 Threads7,825 Posts
Official Starfinder RPG Bug...
September 25th, 2023, 23:42 by madman
Traveller (33 Viewing)
This forum covers any edition of Traveller, including the 1E version and the 2E versions by Mongoose which are available as Official Rulesets.527 Threads6,685 Posts
How do you set range for ship...
September 22nd, 2023, 21:28 by Sternenfahrer
World of Darkness (VTM/Werewolf/Hunter) (52 Viewing)
Discussion for the official 5th Edition ruleset.92 Threads1,165 Posts
September 24th, 2023, 08:30 by Vincent
Other Game Systems (562 Viewing)
2,528 Threads42,399 Posts
- 13th Age,
- Advanced Fighting Fantasy,
- Against The Darkmaster,
- Alien RPG,
- Basic Roleplaying (BRP),
- Conan 2d20 RPG,
- CoreRPG (Generic Ruleset),
- Cypher System,
- Index Card RPG,
- MoreCore Rulesets,
- Mutants & Masterminds,
- Old School Essentials,
- Rolemaster Classic,
- Shadow of the Demon Lord,
- Symbaroum RPG,
- Vaesen,
- White Box OSR
Dungeon Crawl Classics Role...
Today, 17:24 by leozelig
Armory (campaigns, modules, rulesets, maps and tokens) (251 Viewing)
A board for campaigns, modules, rulesets, maps, tokens and other community creations.
Sub-Forums:3,367 Threads63,637 Posts
Today, 15:33 by Spelledarkonto
The Workshop (62 Viewing)
The place to discuss modifications and the creation of house rules and new rulesets.4,752 Threads38,096 Posts
Today, 16:46 by Moon Wizard
The Gallery (23 Viewing)
User submitted Fantasy Grounds screenshots303 Threads2,777 Posts
June 4th, 2023, 05:36 by Kelrugem
The House of Healing - Classic (92 Viewing)
Customer support
The place to find help for technical problems running Fantasy Grounds Classic7,550 Threads55,373 Posts
June 9th, 2023, 06:23 by Varsuuk
What's Going On?
Currently Active Users
There are currently 6175 users online. 80 members and 6095 guests
Most users ever online was 6,882, November 21st, 2020 at 03:18.
- 0wen2477,
- Alanabsed,
- amanwing,
- Armadillo,
- astariaxv,
- AWroe,
- BangsNaughtyBits,
- Baylow,
- BeardedTrafficLight,
- BelleMuerte,
- Birger Tucholski,
- Blahness98,
- Blysill,
- bmos,
- Bonnie,
- boromir96,
- BroodWolfie345,
- Brotherkelly,
- brysheffie,
- ChaosChuck,
- CincyBrandon,
- Ckaleb,
- CrookedKnight,
- Curtiswor,
- Cyphon34,
- dec1conan,
- devilspork,
- EdNarrador,
- ElusivePanda,
- FedeBerserk,
- fredpope,
- Garou,
- Honken,
- InertOptimism,
- johnhalo,
- ju95,
- JustinFreitas,
- Killakia,
- leozelig,
- lokiare,
- Lynnx333,
- Machivellimoo,
- Macquarm,
- Moon Wizard,
- Naplam,
- nephranka,
- Noneitor,
- NuclearMonkey,
- Nyarly Dude,
- OB1Sean,
- OrMtnMan,
- Pharoid,
- pindercarl,
- pokeblock,
- Ram Tyr,
- ReverendoJones,
- Rudakus,
- sailanulendil,
- sfcspencer,
- shadyoats,
- SoloKaiser,
- SpaceMonkeyAR,
- stoneaxecommander,
- superteddy57,
- SylvanSnake,
- Talen,
- tehveihlator,
- TheGMSource,
- thenamelessthree,
- Thomas Kopp,
- Trenloe,
- tschenks,
- ValerionWolf,
- wilconran,
- WoodmanX,
- Xarax,
- Zacchaeus
Spam-O-Matic Statistics
96633 Spammers Denied Registration
1671 Spammers Permanently Banned
1716 Spammers submitted to StopForumSpam
399 Spammers submitted to Akismet
1838 Spammy Posts Automatically Moderated
Fantasy Grounds Message Boards Statistics
- Threads
- 71,009
- Posts
- 674,394
- Members
- 439,962
Welcome to our newest member, EdNarrador
Latest Blog Entry, Dungeon 23 by mhorgunn in Blog Rialacha Teach Mhorgunna


text:
Baoshan Iron & Steel Co. Ltd. (Baosteel) placed an order with Siemens VAI Metals Technologies to equip an electric arc furnace (EAF) in its Shanghai facility with a refining combined burner (RCB) system. The aim of the project is to increase furnace productivity while reducing energy consumption. According to Siemens, installation of the RCB system will help reduce electrical energy consumption per metric ton of steel by up to 10%. Siemens' scope of supply includes burners, modular front plates and valve stands for gas, oxygen and nitrogen. The modernized EAF will resume production in 2010 after a short down time.
Siemens VAI Metals Technologies commissioned a 4,100-millimeter plate mill for Wuyang Iron and Steel Co. Ltd. The new rolling mill will boost the previous system's capacity from 1 million metric tons to 1.6 million metric tons of steel plate per year. The mill will be capable of producing 900- to 3,600-millimeter-wide plate with thicknesses ranging from 6 to 150 millimeters.

subset: commoncrawl


text: In open-plan offices, workstation partitions are particularly useful for dividing workstations and guaranteeing the privacy of those who use them. The panels can be placed on the floor, up to a height of 1.50-1.70 m, or between the desks. The panels can be equipped with tracks to hang objects or even a PC monitor. Partition panels are also used to create more complex spatial configurations, easily adapting to all spaces. The sound-absorbing panels for workstations combine functionality, thanks to sound-absorbing properties, to aesthetics, with original shapes, smooth or textured surfaces, intense colors that give the open space an unparalleled liveliness.


text:
How to Choose the Lighting for a Freshwater Aquarium
- Published in Lighting
- Be the first to comment!
The light the plants are using for photosynthesis must help you answer the question how to choose the lighting for a freshwater aquarium. Usual household lights are not recommended for lighting the tank because they are producing too much heat…Read more...


text:
An article on Paris Photo 2021, with mention of Johno Mellish and THK Gallery.
Read the full piece here.
This website uses cookies
This site uses cookies to help make it more useful to you. Find out more about cookies.
*To prevent this newsletter from going to spam folders, please add us to your contacts list.


text:
The CollaborateUp Formula is a step-by-step process that adapts successful rapid development tools and Lean Startup methodology to focus creativity and jump-starts collaboration. Using our formula results in fully developed, testable solutions with clear, measurable outcomes that stakeholders can use to evaluate how well they've achieved their goals.
Watch the video:
Getting the right people in the room.
Getting participants to understand the problem in the same way.
Institutional Commitment
Giving people time for their teams to decide if they're "in" or "out" and if "in" what they can bring.
Reconvening in a set period of time to develop outcome-specific ways of testing concept solutions.
Launching prototypes with specific, testable outcomes.
Collecting and spreading data in compelling ways that motivate action.


text:
She always understands the assignment.
Rihanna has rewritten the rules of beauty and fashion so many times that you could basically say it's a hobby of hers. And this year has certainly been no exception: Since revealing she's expecting a child with A$AP Rocky back in January, the singer-slash-entrepreneur has been credited with pioneering the "sultry" pregnancy look, a style that went on to dominate this year's Paris Fashion Week and even the cover of Vogue.
Thus, it's no surprise that Rihanna's red carpet glam so regularly breaks the internet — especially when it comes to the Met Gala. Along with notable outfits like a menswear tuxedo and a lengthy princess gown (and so much more), Rihanna's Met Gala makeup and hair looks have equally spurred dropped jaws and heart eyes to all who have caught sight of her. And so, since the 2022 Met Gala is just around the corner (aka next week!), fans are awaiting the daring entrepreneur's debut of yet another show-stopping ensemble and iconic beauty moment.
Be sure to tune in on Monday, May 2, for what will surely be a visual feast. In the meantime, keep scrolling for a look back at Rihanna's best Met Gala makeup and hairstyles that we can't stop thinking about.


text: 149 years ago today, the St Peter's was consecrated as the new parish church for Lancaster; it was raised to Cathedral status with the foundation of the Diocese of Lancaster in 1924. Each year the feast of the Dedication is marked on the Sunday nearest to the anniversary. Tomorrow the Dedication of the Cathedral is celebrated with Mass at 10:30am, a parish lunch and sung Vespers at 4:40pm. Both our Bishops will be with us all day, and Bishop Campbell will preach at both Mass and Vespers. Blog readers - like everone else - are warmly invited to take part in the day. Vespers offers a chance for those outside of the Cathedral parish to take part. If you are free tomorrow afternoon, why not come along and celebrate this annual feast with us?


text:
Manufacturer PSA Group has acquired an interest in parking and car rental start-up TravelerCar, for an undisclosed amount.
The move is part of PSAs 'Push to Pass' strategy, which involves it investing in mobility start-ups. PSA has committed 100m in venture capital to invest in mobility.
TravelerCar offers three types of services at airports, train stations and city centres:
– A free parking tool for car owners who make their vehicles available for rent. Car owners are remunerated if their vehicle is rented.
– Advantageous-price parking solution for owners who prefer not to share their vehicle.
– A reduced-rate car rental option for individuals provided through TraverlerCar rental agencies.
The company was founded in 2012, and has a network of 80 agencies, and over 100,000 users in six countries: France, Spain, the Netherlands, Germany, Switzerland and Belgium.
This isn't the first start-up PSA Group has invested in this year, having invested 18m in Koolicar in April.


text:
Steph Twell added to Antrim International Cross Country field
Last updated on .From the section Athletics
Former winner Steph Twell will race in the Antrim International Cross Country event at Greenmount on 14 March.
Twell, who won the Antrim event as a 19-year-old six years ago, is back in form after being sidelined for two years because of ankle fractures.
The Aldershot athlete, who won 1500m bronze at the 2010 Commonwealth Games, helped Britain take European Cross Country team gold in December.
Thomas Ayeko, who won the men's race in 2013, will also compete in Antrim.
The Ugandan finished second behind World Cross Country champion Japhet Korir at Greenmount last year.
Korir, 21, was the first defending World Cross Country champion to compete in the Northern Ireland event.
The Kenyan, who is not in his country's World Championship team, will again race at Greenmount.
The event will be held concurrently, with with financial constraints meaning Athletics Northern Ireland opted to stage the two meetings together.
Athletes will be competing for a prize fund of just under £10,000, with £1,650 going to the men's and women's winners.
Twell secured a hat-trick of European Junior Cross Country titles from 2006-8 before earning her Commonwealth Games medal when representing Scotland in 2010.
After a series of ankle fractures she returned in 2013 and finished seventh at the European Cross Country in December, helping Britain take team gold.


text:
A California mother is warning others after reportedly finding glass in a beef and bean burrito that her daughter ate.
Tracey Brintle told KNSD that she purchased Tina's Beef and Bean Burrito from a 99ȼ Only Stores in Santee two weeks earlier. She said she gave the burrito to her daughter, Kayla, and heard a crunching noise as she ate it.
"And I saw what's left on her plate and I saw that there was glass," Brintle recalled.
The mother reportedly took her daughter to the emergency room, where she was found to be okay. Afterward, she said she reached out to the two 99ȼ Only Stores in Santee in addition to the company that makes the burrito.
According to KNSD, a representative from Tina's Brand Burritos said they would send the mother a box to send the burrito back to the company so they can test it. As of Friday, the box hadn't arrived but the company reportedly called the mother to assure her that it was in transit.
While it's unclear how glass shards made their way into the burrito, Brintle said she's worried that other people might be at risk as she waits for the company to conduct their testing.
"I'm sure that batch is still available in stores because I only bought it in the middle of August," Brintle told the news station.
"And it needs to be pulled off the shelves."
According to their website, Tina's Brand Burritos are sold at grocery giants all over the country. In light of the incident, the 99ȼ Only Stores in Santee told KNSD that they've pulled the item from their shelves.
Meanwhile, Tina's Brand Burritos has declined to publically comment on the ordeal.
[Featured Image: KNSD video screengrab]


text:
Build reports like Created vs Resolved vs …, etc. Compare the trend of different date fields defined in 'Data Source' date range and sync them on the x-axis timeline using 'Display by': 'Range Date' option.
Please find configuration steps to utilize the feature.
Step 1: Add Data Source with date range based on 'Created' date field
Step 2: Add Data Source with date range based on 'Resolved' date field for the same period. Repeat the same action with other date fields e.g. 'Progress Started', 'Status Category Change', etc. as given the in the sample config.
Step 3: Select 'Range Date' field for 'Display by'. It is special field that sync on the same x-axis timeline all values from the date fields defined into the data sources in the sample case the JIRA issue date fields: 'Created', 'Resolved', 'Progress Started', 'Status Category Change'.
Step 4: Set Group by 'Data Source' to display distinctive trend for each data source based on its respective date field used for Date Range.
Step 5: Select Cumulative mode that will show the accumulated data with each x-axis item. In the sample case that data will be aggregated by week.
Recording: Please check following recording with 'Date range' feature usage:


text:
Copy the page URI to the clipboard
Osborne, Francesco; de Ribaupierre, Helene and Motta, Enrico
URL: http://ekaw2016.cs.unibo.it/
In recent years we have seen the emergence of a variety of scholarly datasets. Typically these capture 'standard' scholarly entities and their connections, such as authors, affiliations, venues, publications, citations, and others. However, as the repositories grow and the technology improves, researchers are adding new entities to these repositories to develop a richer model of the scholarly domain. In this paper, we introduce TechMiner, a new approach, which combines NLP, machine learning and semantic technologies, for mining technologies from research publications and generating an OWL ontology describing their relationships with other research entities. The resulting knowledge base can support a number of tasks, such as: richer semantic search, which can exploit the technology dimension to support better retrieval of publications; richer expert search; monitoring the emergence and impact of new technologies, both within and across scientific fields; studying the scholarly dynamics associated with the emergence of new technologies; and others. TechMiner was evaluated on a manually annotated gold standard and the results indicate that it significantly outperforms alternative NLP approaches and that its semantic features improve performance significantly with respect to both recall and precision.
Viewing alternatives
Download history
Item Actions
- Item ORO ID
- 47332
- Item Type
- Conference or Workshop Item
- Keywords
- Scholarly Data; Ontology Learning; Bibliographic Data; Scholarly Ontologies; Data Mining
- Academic Unit or School
Faculty of Science, Technology, Engineering and Mathematics (STEM) > Knowledge Media Institute (KMi)
Faculty of Science, Technology, Engineering and Mathematics (STEM)
- Research Group
- Centre for Research in Computing (CRC)
- Depositing User
- Francesco Osborne


text:
EUROPCAR is the car rental company with highest customers' rank in Roquetas De Mar with a rating average score of 8.4/10, based on 4208+ customer reviews. The cheapest vehicle from EUROPCAR is Toyota Aygo of Mini car rental class for £28.52 per day.
Plaza De La Estacion, S/n, Estacion Intermodal, Almeria, 04006, An
Plaza De La Estación, S/n, Estación Intermodal, Almería, 04006, An
Plaza De La Estacion Sn Estacion De Tren Y Autobus, Almeria, 04006
Terminal De Llegadas, Almería Airport, Ctra. Níjar Km 9 , Almeria, 04130
If you plan to rent a car in Roquetas De Mar, it might be worth considering other nearby locations to see if you might find a better deal or wider range of cars to better suit your needs. As many as 15% of our customers end up renting a car in a nearby location to their original search as they found a cheaper deal or better rental car.
Get the latest travel inspirations and deals from BmiBaby semimonthly with your email. You can unsubscribe at any time.


text:
Two teenagers were spotted shooting at geese with a catapult on a river in Mitcham .
The RSPCA has said the two males - one aged 17 and the other aged 19 - fired the weapon at geese on the River Wandle near London Road, Mitcham on June 20.
While no birds are thought to have been injured, it is believed this is not the first time geese in Mitcham have been shot at.
The matter has been reported to police and the RSPCA are appealing for witnesses.
All wild birds are protected under the Wildlife and Countryside Act 1981 and it is illegal - except under licence - to take, injure or kill wild birds or interfere with their nest or eggs.
The maximum penalty, if found guilty, is six months in prison and/or an unlimited fine.
RSPCA Inspector Francesca Tambini said: "While details are quite limited, we have been made aware that two youths were seen firing catapults at geese along a stretch of river in Mitcham.
"There have been reports that this was not the first time this has happened.
Follow reporter Sam Truelove on social media
Do you have a story? You can get in touch, in complete confidence if necessary, below:
Follow Sam, or drop him a direct message, on Twitter here.
Follow his Facebook page here.
You can read more of his stories here.
Email him on email@example.com.
Keep up to date with the latest breaking news here.
Like the MyLondon Facebook page and follow MyLondon on Twitter
"The first youth was described as an adult male around 5ft 7in tall with black hair, around 19-years-old and of slim build. The second was described at 5ft 5 in tall with lighter hair and around 17 years old."
Anyone with information is asked to call the RSPCA inspector appeal line on 0300 123 8018.
Want more news? Go to the My London homepage.
Got a story? Email firstname.lastname@example.com.


text:
Tesla Model X (2015-2020) (Front and Rear) Poster
- Regular price
- Sale price
Product Details
Poster print of the Tesla Model X. The Tesla Model X was designed from the ground up to be the safest, most exhilarating SUV on the road. It has unparalleled performance and to top it all off, it is electric!
This print will look absolutely beautiful in your home, office, or garage and would make the perfect gift for a Tesla or car lover!
Frame and mat not included.
Paper Type
Metallic Paper: This high-gloss, metallic pearlescent photo paper will make the print colors appear bolder and more saturated with a brilliant, almost luminescent quality.
Satin Paper: This brilliant bold white satin paper is a traditional premium paper that will display the full color gamut of the print with a luster finish.
Every print is custom made to order on premium 68lb satin or metallic photo paper using professional Epson printers and inks. These high quality fine art prints have incredible detail, resolution and vibrancy. There is a ¼ inch border around the print.
Product color may slightly vary due to monitor calibrations and settings.
We ship worldwide from Canada. We offer free standard shipping to USA.
In order to minimize shipping times, we transport our prints across the border 3 to 5 times per week and ship with USPS first class (unless a faster shipping carrier is available). The whole process takes approximately 5 to 10 business days.
Unhappy with your product? We offer a 30 days money back guarantee.
Product damaged during shipping? We will send you a new one immediately!


text:
Super Max's Hero Surprise is complete and ready to go! This touching story about a military kid who receives a surprise visit from a family member who she thought was deployed, will hit you in the feels and won't let go.
You can find this book on Amazon Here
Formats includes hardcover, softcover, and Kindle.


text:
Sacred Creativity + Inspiration
Holiday Gift: A Pandemic Proof Life
During these troubling times, I feel that we need our loved ones more than ever. This is why it was particularly difficult this past December. What used to be a big, loving fiasco of 30 or so family members turned into a very small pow-wow of just my two brothers and their small families. It…Read More
Does the Creative Writing from your Past Still Haunt You?
I remember being so proud of my first compilation of poetry and short stories. I still am. Only 23 years old at the time, independently publishing a book and receiving a couple awards was a huge feat. Now, as I took forward and prepare to share new stories with the world, my past haunts me.…Read More
Succeeding on Purpose for my Readers
"Successful people are not gifted; they just work hard, then succeed on purpose." – G.K. Nielson Why would you leave your life-goals to chance? Being a passive bystander to your career isn't likely to help make your goals come true. I don't even know if it would be accurate to say I'm a gifted storyteller.…Read More
Creating Is A Sacred Task
I've always been committed to publishing my long awaited first novel. I feel absolutely awesome because now I've finally created the time to push things forward. Saying there's "no time" to do what you're passionate about it just an excuse. How you spend your time is a choice. On Twitter, one of the favorite questions…Read More
What Is The Best Medium For Storytelling?
Writer's Digest published What a Novel Can Do That Film and TV Can't that's somewhat one-sided towards novels in terms of being the best medium for storytelling. Yes, Novels offer a ton more flexibility, but film has some pretty powerful benefits too. As a storyteller, my stories are currently in book form. Why? Because I'm…Read More
Clues Into Your Purpose and What Brings You To Life
When it's so cold outside, it's a perfect day to stay inside and write! My perfect day involves double stuffed Oreo cookies, family, books, stories, movies, and some sort of outreach that helps people. Think about your perfect day. What does a "perfect" day look like to you? When you're aware of what your perfect…Read More
Fitting In Things That Are Important, But Not Always A Priority
I'm about to take a flight out of town this morning. Taking my writing laptop with me. I NEVER get writers block. It's always about not having the time to get out what's in my head! I replay it over and over again in my mind until I have a chance to write it out.…Read More
For Every Excuse, There's A Solution to Get Through
The royal newlyweds look so happy! If I was married to royalty and didn't have to worry about finances; guess what I would do most of the day…. ::hint-hint create awesome stories!:: Thankfully, no one has to wait for a rich partner in order to afford to do the Work they love. Yes, I know…Read More


text:
Exclusive: Maruti in top gear before BS6 dateline, hopes to score big in 2020
At a time when many auto manufacturers are wiping brows over their respective stockpiles of BS4 vehicles, Maruti Suzuki is placed well to embrace the transition to BS6 fuel-compatible vehicles. With as many as eight launches in 2019 keeping the April 2020 dateline for BS6 in mind, the country's largest automaker is hoping to keep the momentum going and going strong.
In an interview with HT Auto on the sidelines of HT Brand Studio Live, Shashank Srivastava - Excecutive Director at Maruti Suzuki - elaborated about how the transition is hardly a speed bump for the company and that the product portfolio remains robust. I think the transition from BS4 to BS6 will become extremely critical, especially when you look at diesel vehicles where many manufacturers have said they won't be transitioning to BS6 diesel at all," he said. "We have already introduced eight of our models which are BS6. We in fact introduced the Alto and the Baleno in April 2019, almost a year in advance. Subsequently the WagonR, the Swift, Dzire, Ertiga, XL 6 and the S-Presso. Now these models are not small selling models. They cover almost 70% of our sales in petrol."
Avoiding fire sales
Srivastava said that Maruti Suzuki's push towards BS6 vehicles has helped the company keep BS4 stocks in check and that massive discounts to clear old stock may not be required at all. "Our strategy has been to introduce it (BS6-complaint cars) earlier and keep pushing and monitoring the stock of BS4 vehicles so that when the transition does come, we don't have to necessarily go for a fire sale which we saw when there was this transition in two-wheelers and trucks," he said.
Also check these Vehicles
Diesel in the dumps?
That Maruti is determined to veen away from diesel has also been evident over the past several months. Srivastava said that a number of factors have contributed to this shift in strategy. "We will be moving out of diesel because cost of conversion from BS4 to BS6 (in diesel) is extremely high," he said. "While we move away from diesel for gasoline vehicles, it is only possible to introduce BS6 vehicles earlier (than the April deadline) in gasoline. It is not possible in diesel because if you have a BS6 diesel (vehicle) and only BS4 fuel available, it doesn't work. However, in gasoline, it is fuel agnostic which means that a BS4 gasoline (vehicle) can work on BS6 fuel and BS6 gasoline vehicle can work on BS4 (fuel). So that has been our basic thrust."
Technological and cost challenges aside, Srivastava says that even consumers have shown the maturity to embrace cars with cleaner fuel systems. " Let me tell you that BS6 has been very well received. One of the things that our analysts have been saying is that this (move to BS6) entails an increase in prices, which we have done, even in petrol vehicles. There was always this risk that consumers reject it because a cheaper BS4 is available. But what we have found is that consumers have liked BS6, the concept and are preferring the BS6 vehicles," he said. "(Also) I think for most vehicles, especially the smaller cars, consumers - who are very sensitive to price -will probably not prefer diesel at all."
This may well be why Maruti Suzuki is lining up the Vitara Brezza petrol as its next big-ticket launch. The Brezza has been a volume player for the company in the sub-compact segment but has been hurting in recent times due to its diesel-only avatar. Competition from Hyundai Creta, Kia Seltos and MG Hector - cars a segment above but with petrol options - has not been forgiving either.


text:
Brand Name: PLBBFZ
Material: polyester
Material: Rayon
Material: Lace
Material: Mesh
Origin: CN(Origin)
Dresses Length: Ankle-Length
Collar: O-neck
Sleeve Style: Regular
Built-in Bra: No
Model Number: K1-2092
Pattern Type: Patchwork
Silhouette: Ball Gown
Gender: Girls
Sleeve Length(cm): Full
Style: Formal
Fit: Fits true to size, take your normal size
Age Range: 4-6y
Age Range: 7-12y
Decoration: Lace
Season: Winter
Department Name: Children
Size: 120/130/140/150/160-170
Occasion: Evening,Party,Show,Tv,Birthday,Wedding,Bridesmaid
Season: Spring,Summer,Autumn,Winter
Kids Dresses for Girls: Dresses Girl
Birthday Tutu Dress: Flower Girl Dress
children's dress: girls clothing 10 12 years
child girl princess dress: girl evening dress
bridesmaid dresses for kids: prom evening dress
Size Chart
This size chart is a standard size. When there is a product size chart on the product detail page, please use the product size chart.
The general delivery time of our website is 1-3 working days.
After delivery, it will generally be delivered within 7-15 working days To US & UK.
We offer faster logistics options.
You will receive a delivery notice email containing logistics number and tracking link after delivery
We provide logistics to most countries and regions around the world. There are different prices and shipping times according to different countries and addresses.
We provide thoughtful after-sales service.
If you have any dissatisfaction within 30 days after you receive the package, please feel free to contact us for a return or exchange plan.
We will tailor the service to your 100% satisfaction according to your situation.
Customer reviews
I LOVE THIS SHIRT!! I'm 140 pounds and a 36C bra size for reference! It fits perfect around my body and you can tie the straps tighter for extra support, slightly see through but not bad, could also be because I got a light color, fast shipping!! Buying the black one now thanks seller!!!


text:
A funky design with a lot of sophistication. This RMC Martin Ksohoh 1001 model Japanese indigo raw denim jeans will let you crop up on the style radar. The red line selvedge denim has custom hand stitched back pockets. The back pockets are decked with extraordinary hand embroidered red signature logo right pocket, and hand embroidered yellow signature logo left pocket. The awesome skull designs give a funky zeal to the jeans. SKU-RMC3744
- Painted metal buttons
- Five pocket, Button fly
- Copper rivets, Red tab
- Leather patch on waistband
- Individual ID serial number
- 100% Cotton
- Made in Japan
We ship with couriers including Fedex UK, DPD, UK Mail & Royal Mail offering a service which ensures your purchases arrive safely, securely and promptly. When your order is dispatched you will receive an email enabling you to track the status of your consignment online- full transparency all of the way from our store to your door
Flat Shipping Rate Per Order Per Address
UK Mainland Delivery Signed For £10.00
UK Off-mainland Delivery Signed For £30.00
Channel Islands, Northern Ireland and Outer Hebrides
Delivery Zone R Signed For International £39.00
Belgium, Ireland, Luxembourg, Netherlands
Delivery Zone S Signed For International £39.00
Andorra, Austria, Denmark, Faroe Islands, Finland, France, Germany, Greece, Greenland, Italy, Monaco, Portugal, Spain, Sweden, Vatican City
Delivery Zone T Signed For International £39.00
Bulgaria, Cyprus, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Malta, Poland, Romania, Slovak Republic, Slovenia
Delivery Zone U Signed For International £39.00
Canada,Gibraltar, Iceland, Liechtenstein, Norway, Switzerland
Delivery Zone V Signed For International £49.00
Albania, Belarus, Bosnia, Croatia, Macedonia, Moldova, Montenegro, Russia, Serbia, Turkey, Ukraine
Delivery Zone A Signed For International £24.00
United States
Delivery Zone B Signed For International £49.00
Australia, Cambodia, China, East Timor, Hong Kong, Indonesia, Japan, Laos, Macau, Malaysia, Mexico, New Zealand, Philippines, Singapore, South Korea, Taiwan, Thailand, Vietnam
Delivery Zone C Signed For International £59.00
Algeria, Bahrain, Bangladesh, Bhutan, Brunei, Egypt, India, Iraq Republic, Israel, Jordan, Kuwait, Lebanon, Libya, Morocco, Myanmar, Nepal, Oman, Pakistan, Palestine Authority, Qatar, Saudi Arabia, Sri Lanka, Syria, Tunisia, U.A.E, Yemen
Rest of the World Signed For Delivery £69.00


text:
In line with its environmental commitment, Ferragamo has partnered with various logistic providers to offset, through carbon neutral certified projects, all CO2 emissions generated by the shipment of its products; specifically, an agreement with UPS for the products ordered through the eCommerce platform in the United States and a partnership with DHL Express for the eCommerce shipments in Europe.
As of 2016, for all the Italian facilities, Ferragamo has obtained the ISO 14064 Certification concerning the reporting of CO2 emissions, the ISO 14001 Certification, which defines an Environmental Management System and the ISO 50001 Certification, to ensure a more efficient and sustainable use of energy.
Since 2017, the Company has voluntarily participated in the CDP's climate change questionnaire, to favour transparency and accounting of CO2 emissions. In 2022, Ferragamo has been recognized with an B score for its actions to cut emissions, mitigate climate risks and develop the low-carbon economy. Based on the 2022 CDP questionnaire, Ferragamo entered the 2022 CDP Supplier Engagement Leaderboard, ranking that celebrates the leading companies assessed for their ability to engage suppliers on the issue of climate change.
As part of its sustainability strategy, the Company is also committed to searching for sustainable transport solutions through the optimization of employees' transfers and to identifying initiatives capable of reducing environmental impact, such as car sharing and carpooling. Moreover, starting in 2021 the Company signed a partnership with Alphabet, a BMW Group company specialized in the provision of corporate mobility services, for the replacement of the Company's fleet of more than 150 corporate vehicles in Italy with Plug-In Hybrid or Full Electric cars, with the aim of reducing CO2 emissions.


text:
❃ Our gigantic fruit and vegetable plush pillow toy makes the best gift for fruit and vegetable lovers or plushie lovers! An amazing present for anyone during birthdays, Christmas and more!
❃ Our giant fruit and veggie cushion toys can be used as a pillow, cushion, decor and for hugging! They make for a great body pillow and home decor!
❃ Grab one of these today and use it to cuddle while taking a nap or watching TV. Comes in 3 sizes and different types of fruit and vegetable soft toy for you to choose from!
Package includes: 1 x Giant Fruit And Vegetable Plush Pillow Cushion Decor Toy
Shipping time: Due to high demand please allow 2-3 weeks for delivery.
We know it can be stressful buying products online. To help reduce that stress, we offer a full 30 day money back guarantee policy on all of our orders. In addition we provide:


text:
Remember three years ago when an Egyptian young lady wrote Chris Martin a Facebook open letter using Coldplay's lyrics and created a social media frenzy?
The Artist and Founder of Shuffle Designs, Amal Salah, had a dream, and it's basically drawing a huge portrait of Martin, and having it displayed at one of their concerts. Salah promised that the portrait will be different, just like Martin because he's "a sky full of stars." I cried a river reading it; alas we doubt it ever happened.
Yet rest assured dreamers, for the girl with big dreams is now a big name in Egypt due to her visionary and intricate pieces of art. Our Egyptian girl knows what it's like to work with nails. Yes, you read that right! Those ugly silver, occasionaly rusty nails can turn into visions!
"Six years ago, I tried to draw my husband holding my first child in a different way, so I drew them using dots and then I tried to make it a three-dimensional portrait", Amal Salah told us about the beginning of her journey. "I converted these dots to screws on a wooden sheet. I tried all kinds of materials before screws as pins and toothpicks, but settled for screws."
Salah then created a portrait of her favorite movie, Fight Club, to put in her home. Everyone loved it, and that was the beginning of a long series of artistry.
"I made movie collections then started a brand called Shuffle Designs; my aim was experimenting with materials and mixed media," Salah continued. "I created artwork and installations with materials rather than the screws as squared nuts and wires."
Another post by Amal that went viral; other than her letter for our beloved Martin, was the artwork created for the Red Bull office in Cairo. It was out of this world, incredibly accurate, with thousands of details that were nailed perfectly. It took three weeks to be executed using 13,500 nails in the process.
Some of her favorite portraits include one created for French-Lebanese Jazz Trumpeter and Composer, Ibrahim Maalouf during his concert by the Pyramids of Giza. He even mentioned her artwork, that's made of 7,600 nails, on social media later. That in addition to direct-on-wall skyscrapers created for a real estate company.


text:
Attendance policy revisions left to school boards
December 12th, 2013
Omaha, NE — Some Nebraska parents are calling for a change to the school attendance policy.[audio:https://kvnonews.com/wp-content/uploads/2013/12/FINAL1.mp3]
Under Nebraska's current Excessive Absenteeism Law if a school-age child is absent 20 days per year from school and even if all of the absences are the result of a documented illness that makes attendance impossible or are otherwise excused by school authorities, the school attendance officer may report such information to the county attorney.
While parents and advocacy groups such as Nebraska Family Policy Forum and Black Men United want the school attendance law repealed, Nebraska State Sen. Brad Ashford of Omaha said opponents need to look to their local school boards for solutions.
"We've left it up to the schools to determine what the policy is regarding absences,†Ashford said. "It's not about state law changes. I'm not even remotely interested in revising state law.â€
Ashford said disapproval for the policy comes from school officials not dealing with absenteeism in a consistent manner. He said while some schools may have been lax about student absenteeism, others may have taken a more strict approach, which left many families in court.
Justin Wayne, president of the Omaha Public School board, said they are currently reviewing the school's policy. Wayne said the intention of the law is about finding the underlying reason for a child missing school in order to help them get back on track and be successful.
"We're going to make some changes in regard to how we deal with kids who have illness, deal with kids who are gone on vacation. We're going to make it more family friendly to make sure kids are not caught up in a system they don't need to be in,†Wayne said.
Lavon Stennis- Williams is the executive director of Triage, an organization that has partnered with the juvenile court system to assist children who are excessively absent. She said there is a misperception that the county attorney is unthinkingly filing charges against children and their parents because that child has missed a lot of school.
"They at first attempt to resolve it by referring that family to community programs,†Stennis-Williams said. "The other thing we're finding out is that the kids who we're serving are not absent because of illnesses. They are absent because they have just chosen not to go to school. We're also finding many parents who are just enabling them by saying 'Well I've given up. I can't make him or her go to school so I don't try.'â€
Stennis- Williams said solutions need to be made from a neutral ground that focuses on the best interest of the child and not the convenience of parents or the community.
Unfortunately, the solutions that are already in place are affecting minorities and low-income families at a disproportionate rate, according to Sarah Forrest, policy coordinator child welfare and juvenile justice at Voices for Children.
"In 2012 even though white children in our state make up the majority of the population they made up less than half of the children who are filed on in juvenile court for truancy,†Forrest said. "Children and youth of color are more likely to formally enter the juvenile justice system for truancy than they were before the law was passed.â€
Forrest said more than 70 percent of children who miss 20 or more days of school meet the requirements for free and reduced lunch. These statistics could spell trouble for these children in the future, according to Forrest.
"Once a kid becomes involved in the juvenile justice system national research really shows that it can have a lot of negative outcomes for them. It actually makes it harder in terms of educational achievement. It exposes them to a number of risks that we just would rather see those kids not exposed to,†Forrest said.
Ashford is currently drafting a bill to allocate $2 million for schools to develop their own programs to fight truancy. Although he doesn't believe the county attorney can completely be cut out of the picture, he wants to provide more resources to help schools serve students.
"The reason that I don't think you can totally take the county attorney office or the juvenile court system–again these are not criminal offenses these are status offenses. You're supposed to be in school. Therefore, if you're not in school and you have no excuse and the school district can't find you then something has to be done,†Ashford said.
The Omaha Public School board is expected to have a revised attendance policy in place by the beginning of the 2014-2015 school year.
Comments are closed.


text:
Senator Sean Nienow makes tearful apology for "misunderstanding" surrounding Small Business Loan.
"I blew it", admitted Nienow, "I never thought they'd want their money back so badly".
"Apparently, they want to target a high-profile public official that is a month or two behind on payments", said the politician who is more than 30 months behind in his repayment to the Federal Government.
"Do you know what?? Fuck you guys! The fact that I stole all of this money from the government and have ignored their repeated attempts to settle have nothing to do with the fact that I am a Conservative politically-minded adult with a focus on self-responsibility and fiscal conservation".


text:
The Big Problems you'll face while on a Keto Diet.... and how to overcome them
Updated: Sep 30, 2019
3 Reasons why keto isn't working and what you can do to make it work. #1 You're not logging your food. Not logging your food leads to a lot of guessing and that leads to either not having enough fat or to much carbs or fat. Use an app like myfitnesspal to help keep track of your Macronutrients
#2 You're not eating enough vegetables. A lot of people feel that being on a keto diet means only having bacon and eggs and butter. However there is more to it than that, following a keto diet correctly should have huge benefits to your health overall because of the greens you should be incorporating to your diet plus the fiber from those greens help with your overall net carbs. #3 Not having a system to guide you. Many people look up diets online and find pieces of the whole picture. So with any diet not just keto it is important to know the whole process so you can get the results you want and not be stuck in the same place or even gain weight


text:
Hebephilia Frerard. Gerard finds himself attracted to the Neighbor's child, Frank, and when Frank comes over to his house for help one evening, will Gerard do something he'll regret? This will prob...
Category: My Chemical Romance - Rating: NC-17 - Genres: Drama - Characters: Frank Iero,Gerard Way - Warnings: [Y] - Chapters: 4 - Published: 2011-11-13 - Updated: 2014-01-19 - 5411 words
All stories contained in this archive are the property of their respective authors, and the owners of this site claim no responsibility for their contents
Page created in 0.0037 seconds


text:
Article Text
Background: A recent study from our laboratory showed that induction of the multidrug resistance related drug efflux pump ABCG2 contributed to acquired resistance of human T cells to the disease modifying antirheumatic drug (DMARD) sulfasalazine (SSZ).
Objectives: To investigate the duration of SSZ resistance and ABCG2 expression after withdrawal of SSZ and rechallenging with SSZ, and to assess the impact of SSZ resistance on responsiveness to other DMARDs.
Methods: Human CEM cells (T cell origin) with acquired resistance to SSZ (CEM/SSZ) were characterised for (a) SSZ sensitivity and ABCG2 expression during withdrawal and rechallenge of SSZ, and (b) antiproliferative efficacy of other DMARDs.
Results: ABCG2 protein expression was stable for at least 4 weeks when CEM/SSZ cells were grown in the absence of SSZ, but gradually declined, along with SSZ resistance levels, to non-detectable levels after withdrawal of SSZ for 6 months. Rechallenging with SSZ led to a rapid (<2.5 weeks) resumption of SSZ resistance and ABCG2 expression as in the original CEM/SSZ cells. CEM/SSZ cells displayed diminished sensitivity to the DMARDs leflunomide (5.1-fold) and methotrexate (1.8-fold), were moderately more sensitive (1.6–2.0 fold) to cyclosporin A and chloroquine, and markedly more sensitive (13-fold) to the glucocorticoid dexamethasone as compared with parental CEM cells.
Conclusion: The drug efflux pump ABCG2 has a major role in conferring resistance to SSZ. The collateral sensitivity of SSZ resistant cells for some other (non-related) DMARDs may provide a further rationale for sequential mono- or combination therapies with distinct DMARDs upon decreased efficacy of SSZ.
- disease modifying antirheumatic drugs
- multidrug resistance
- sulfasalazine
- ABC, ATP binding cassette
- BCRP, breast cancer resistance protein
- DMARDs, disease modifying antirheumatic drugs
- FCS, fetal calf serum
- IC50, drug concentration required to inhibit cell growth by 50%
- MDR, multidrug resistance
- MRP1, multidrug resistance associated protein 1
- MTX, methotrexate
- NFκB, nuclear factor κB
- Pgp, P-glycoprotein
- SSZ, sulfasalazine
- TNFα, tumour necrosis factor α
Statistics from Altmetric.com
Request Permissions
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center's RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.
- ABC, ATP binding cassette
- BCRP, breast cancer resistance protein
- DMARDs, disease modifying antirheumatic drugs
- FCS, fetal calf serum
- IC50, drug concentration required to inhibit cell growth by 50%
- MDR, multidrug resistance
- MRP1, multidrug resistance associated protein 1
- MTX, methotrexate
- NFκB, nuclear factor κB
- Pgp, P-glycoprotein
- SSZ, sulfasalazine
- TNFα, tumour necrosis factor α
Acquired drug resistance is recognised as a common cause of treatment failure for patients with cancer after sustained treatment with cytostatic drugs.1,2 An important mechanism of acquired cellular drug resistance to anticancer drugs is the overexpression of drug efflux pumps belonging to the superfamily of adenosine triphosphate dependent binding cassette (ABC) transporters.2–6 ABC transporters with an established role in drug efflux and drug resistance include (a) P-glycoprotein (Pgp, ABCB1), which confers resistance preferentially to lipophilic drugs7; (b) members of the multidrug resistance associated protein subfamily (MRP1-6, ABCC1-6), which confer resistance to various anionic charged/glutathione conjugated drugs such as methotrexate (MTX),8 thiopurines,9,10 and steroids5,11; and (c) ABCG2, also known as breast cancer resistance protein (BCRP), a recently identified ABC transporter that confers resistance to amphiphilic drugs, including mitoxantrone and MTX.12,13
In clinical rheumatology, loss of drug efficacy is also noted for patients with rheumatoid arthritis (RA) receiving long term treatment with disease modifying antirheumatic drugs (DMARDs).14–17 Whether this loss of DMARD efficacy is related to the onset of acquired resistance to DMARDs, with mechanisms similar to anticancer drug resistance, is not known.18 Meta-analyses of DMARD treatment termination rates showed that the DMARD sulfasalazine (SSZ)19,20 had a relatively shorter lasting efficacy than other DMARDs, in particular the "gold standard" MTX.14,16–18 In general, lack of efficacy may be related to diminished anti-inflammatory and/or antiproliferative effects of DMARDs against proinflammatory cytokine releasing cells at inflammatory sites.21
To gain insight into the possible mechanism(s) of resistance to the antiproliferative/anti-inflammatory effects of the DMARD SSZ, we previously provoked acquired resistance to SSZ in an in vitro model system of human T lymphocytes by stepwise exposure of CEM (T) cells to gradually increasing concentrations of SSZ.22 This study showed that SSZ resistance in CEM (T) cells was conferred by overexpression of a drug efflux pump—notably, the multidrug resistance transporter ABCG2/BCRP. Owing to enhanced drug efflux in SSZ resistant cells (CEM/SSZ), higher concentrations of SSZ were required to inhibit the secretion of the proinflammatory cytokine tumour necrosis factor α (TNFα).22
In the present study we investigated the stability of the resistant phenotype of CEM/SSZ cells after withdrawal of SSZ in order to establish whether SSZ resistance is slowly/rapidly lost over time and reinducible after SSZ rechallenge. Moreover, we analysed to what extent SSZ resistance affected antiproliferative effects of other DMARDs and anti-inflammatory drugs. The results demonstrated that SSZ resistance, along with ABCG2 expression, was gradually lost over a period of 6 months after withdrawal of SSZ, but rapidly re-emerged, within 2 weeks, upon rechallenge with SSZ. Drug sensitivity was as follows: CEM/SSZ cells displayed lower sensitivity (fivefold) to the DMARD leflunomide, a slightly diminished sensitivity to MTX (twofold), moderately increased sensitivities for cyclosporin A and chloroquine (up to twofold), but a markedly enhanced sensitivity for dexamethasone (13-fold).
Sulfasalazine, leflunomide, chloroquine, phenylmethylsulfonyl fluoride (PMSF), and dexamethasone were purchased from Sigma Chemical Co (St Louis, MO, USA). Protease inhibitor cocktail and Triton X-100 were from Boehringer Mannheim (Ingelheim, Germany). MG132 was from Calbiochem (Germany). MTX was a generous gift from Pharmachemie Haarlem, the Netherlands. Cyclosporin A was a gift from Novartis (Arnhem, the Netherlands). The ABCG2 inhibitor Ko14323 was kindly provided by Dr A Schinkel (Netherlands Cancer Institute, Amsterdam, the Netherlands). RPMI-1640 tissue culture medium and fetal calf serum (FCS) were obtained from Gibco Chemical Co, Grand Island NY, USA.
Cell culture and selection of SSZ resistant CEM (T) cells
SSZ resistant human CEM (T) cells were isolated as described previously.22 In short, human CEM (T) cells were cultured at an initial density of 3×105 cells/ml in RPMI-1640 medium supplemented with 10% FCS, 2 mM l-glutamine, and 100 µg/ml penicillin and streptomycin in a 5% CO2 incubator at 37°C.24,25 Cell cultures were refreshed twice weekly and SSZ was added to the cell culture medium at an initial concentration of 0.4 mmol/l. This concentration of SSZ could be stepwise increased to 1.5 mM SSZ (after 4 months) and 2.5 mM SSZ after a period of 6 months.
Extensive binding of SSZ to plasma proteins (serum albumin) is known to limit its therapeutic effect.26,27 Based on the presence of at least three classes of SSZ binding sites on serum albumin and their association rate constants28 it can be calculated that a protein concentration of about 100 µmol/l in 10% FCS can bind 320 µM SSZ. For the two selected SSZ resistant CEM cells grown in the presence of 1.5 and 2.5 mM SSZ, this would imply that 21% and 13% of SSZ, respectively, is protein bound.
It should be recognised that CEM cells are of T cell leukaemic origin, proliferating with a doubling time of 26–30 hours. Thus CEM cells may not fully representative for normal T cells or T cells applicable to RA. However, CEM cells may serve as a valuable in vitro model system for RA research as they respond to T cell stimuli, producing proinflammatory cytokines like TNFα.22 Furthermore, CEM cells have been exploited to disclose resistance mechanisms to MTX that are clinically encountered.24,29–31
Antiproliferative effects of DMARDs and other drugs were analysed by plating 1.25×105 cells/ml of parental CEM (T) cells, CEM/SSZ1.5, and CEM/SSZ2.5 cells (in the absence of SSZ) in individual wells of a 24 well plate containing up to 50 µl of drug solution. Inhibition of cell growth was determined after 72 hours' incubation by counting cells with a haemocytometer and cell viability by trypan blue exclusion. The drug concentration required to inhibit cell growth by 50% compared with control growth is defined as the IC50 concentration.
Western blotting
For analysis of expression of ABCG2/BCRPand ABCC1/MRP1, cells were harvested in the mid-log phase of growth and washed three times with ice cold Hepes buffered saline, pH 7.4. Total cell lysates of 107 cells were suspended in 500 µl of lysis buffer containing 50 mM Tris-HCl (pH 7.6), 5 mM dithiothreitol, 20 µl protease inhibitor cocktail (one tablet/ml H2O), 20% glycerol, and 0.5% NP-40. The suspension was sonicated (MSE sonicator, amplitude 6, for 3×5 seconds with 30 seconds time intervals at 4°C) and centrifuged in an Eppendorf microcentrifuge (10 minutes, 14 000 rpm, 4°C). Protein content of the supernatant was determined by Biorad protein assay.32 Fifty microgram of total cell lysates was fractionated on a 7.5% polyacrylamide gel and transferred onto a nitrocellulose membrane. The nitrocellulose membranes were preincubated overnight at 4°C in blocking buffer (5% Biorad Blocker in TBS-T (10 mM Tris-HCl, pH 8.0, 0.15 M NaCl, 0.1% Tween-20) to prevent aspecific antibody binding. After blocking, the membranes were incubated for 1 hour at room temperature with the primary antibodies for the multidrug resistant (MDR) pumps ABCG2/BCRP (BXP21, 1:400) and MRP1 (MRPr1, 1:500) as described by Scheffer et al.32,33 As control for protein loading, β-actin (Chemicon International, Ca, USA: 1:3000) was used. After three washing steps with TBS-T, membranes were incubated for 1 hour with horseradish peroxidase labelled antirat/mouse (Dako; 1:2000 for ABCG2/BCRP and ABCC1/MRP1, and 1:3000 for β-actin) as secondary antibody. Detection of the antibody binding was measured by enhanced chemiluminescence according to the manufacturer's instructions (Amersham International, Buckinghamshire, UK). Protein levels were determined by densitometric scanning (GelDoc and Molecular Analyst, Biorad Laboratories) of the x ray films (Hyperfim ECL, Amersham International, Buckinghamshire, UK).
Statistical analysis
Statistical significance of differences was analysed by analysis of variance using SPSS 9.0 computer software. A p value <0.05 was considered to be significantly different.
Onset and stability of SSZ resistance in human CEM (T) cells
Acquired resistance to SSZ in human CEM (T) cells could be provoked by culturing cells in stepwise increasing concentrations of SSZ.22Figure 1A (point A) shows the antiproliferative effect of SSZ (IC50: concentration for 50% growth inhibition) for CEM (T) cells at the initial dosing of 0.4 mM SSZ, and for CEM (T) cells that were grown in the presence of stepwise increasing concentrations of SSZ. After a period of 4 months, CEM (T) could be maintained at an IC50 concentration of 1.5 mM SSZ (CEM/SSZ1.5) which was about fourfold higher than parental CEM (T) cells. When CEM/SSZ1.5 cells were grown in the presence of 1.5 mM SSZ for another 2 months, the IC50 value slightly increased to 1.7 mM (fig 1A, point B). When, in parallel, CEM/SSZ1.5 cells obtained after 4 months were exposed to further increasing concentrations of SSZ for 2 months, eventually CEM/SSZ2.5 cells were obtained that could grow in the presence of 2.5 mM SSZ (not shown).
To establish whether the SSZ resistance in CEM/SSZ1.5 cells is a transient or stable phenotype, CEM/SSZ1.5 cells (at point B) were further grown in the absence of SSZ, and IC50 values for the CEM/SSZ1.5 cells were monitored over time. After 1 week in the absence of SSZ, IC50 values for SSZ dropped by 40–50% to stay at this level for up to 4 weeks. From this point on, IC50 values for SSZ gradually declined to reach ultimately the original levels of SSZ sensitivity of parental CEM (T) cells (point C). To assess whether SSZ resistance would be reinduced upon exposure to SSZ, revertant CEM/SSZ1.5 cells were re-exposed to 1.5 mM SSZ. Within only 2.5 weeks' exposure to SSZ (D), revertant CEM/SSZ1.5 cells resumed their original level of SSZ resistance as seen at point B. These results indicate that although SSZ resistance in CEM/SSZ is transiently lost over a period of 6 months, rechallenge of revertant cells with SSZ rapidly reinduces resistance to SSZ.
Expression of MDR transporters ABCG2/BCRP and ABCC1/MRP1 in CEM (T) and CEM/SSZ cells
Initial studies from our laboratory22 reported differential expression of MDR proteins upon development of SSZ resistance in CEM/SSZ cells: induction of ABCG2/BCRP and down regulation of ABCC1/MRP1 expression. Figure 1B illustrates the expression of ABCG2/BCRP and ABCC1/MRP1 at the various times A–D in fig 1A. Parental CEM (T) cells (point A, fig 1A) exhibited undetectable levels of expression of ABCG2/BCRP protein, but had an appreciable level of ABCC1/MRP1. In contrast, SSZ resistant CEM cells isolated at 1.5 mM SSZ (CEM/SSZ1.5 cells) (fig 1A, point B) showed a marked induction of ABCG2/BCRP expression and down regulation of ABCC1/MRP1 expression. After withdrawal of SSZ from the cell culture of CEM/SSZ1.5 for a period of 6 months (fig 1A, point C) ABCG2/BCRP and ABCC1/MRP1 expression reverted to the original levels of parental CEM (T) cells. Notably, when revertant CEM/SSZ1.5 were re-exposed to 1.5 mM SSZ for 2.5 weeks (fig 1A, point D), ABCG2/BCRP expression was rapidly up regulated, while ABCC1/MRP1 was again down regulated. As a control, fluctuations in the expression of ABCG2/BCRP paralleled the growth inhibitory effects (IC50 values) for the cytostatic drug mitoxantrone, which is a known substrate for efflux by ABCG2/BCRP6,34 (data not shown).
Because fig 1A showed that changes in IC50 values for CEM/SSZ1.5 cells were particularly noted within the first 10 weeks after withdrawal of SSZ (fig 1A, point B→C), we fine tuned the analysis of IC50 values for SSZ and changes in expression of ABCG2/BCRP and ABCC1/MRP1 during this period of 10 weeks. IC50 values for SSZ dropped by about 40–50% after growth of CEM/SSZ1.5 cells in the absence of SSZ for 1 week (fig 2A). From this point on, IC50 values for SSZ only slowly declined. At 70 days after withdrawal of SSZ from CEM/SSZ1.5 cells, resistance to SSZ could still be noted compared with parental CEM (T) cells. Figure 2B shows the expression of ABCG2/BCRP and ABCC1/MRP1 in parental CEM (T) cells (lane A) compared with CEM/SSZ1.5 cells before (lane B) and after withdrawal of SSZ for 3 days, 7 days, 4 weeks, and 10 weeks (lanes C–F, respectively). ABCG2/BCRP protein expression in CEM/SSZ1.5 cells appeared to be stable for at least 4 weeks after withdrawal of SSZ, after which a diminished, but still detectable, level of expression could be seen after 10 weeks. ABCC1/MRP1 expression, which was down regulated in CEM/SSZ1.5 cells in the presence of SSZ, was rapidly reinduced within 3–7 days after withdrawal of SSZ, even overshooting the level of ABCC1/MRP1 expression in parental CEM (T) cells after 70 days of SSZ withdrawal from CEM/SSZ1.5 cells. These results indicate that ABCG2/BCRP and ABCC1/MRP1 follow an inverse pattern of expression after SSZ exposure/withdrawal.
Given the apparent discrepancy of the rapid partial loss of SSZ resistance within 1 week of withdrawal of SSZ from CEM/SSZ1.5 cells (fig 2A) and the stable expression of ABCG2/BCRP during this period (fig 2B, lanes B–D), we further investigated the functional contribution of ABCG2/BCRP in SSZ resistance by blocking ABCG2/BCRP with a specific inhibitor, Ko143.23 Blocking of ABCG2/BCRP reversed SSZ resistance in CEM/SSZ1.5 cells by 50–60%, but not completely, to parental CEM (T) cell sensitivity (fig 2C). After growth of CEM/SSZ1.5 cells in the absence of SSZ for 4 weeks, when IC50 values for SSZ had stabilised at about 50% of the original CEM/SSZ1.5 cells, Ko143 fully reversed the residual SSZ resistance of CEM/SSZ1.5 cells to the SSZ sensitivity of CEM (T) cells (fig 2C). These results indicate that SSZ resistance in CEM/SSZ1.5 is mediated by at least two components, each contributing about 50%. One component, is rapidly lost within one week after withdrawal of SSZ, the other component, which stabilised after 1–4 weeks' growth of CEM/SSZ1.5 cells in the absence of SSZ, can be fully accounted for by ABCG2/BCRP. The latter component is then gradually lost over period of 5 months' culture in the absence of SSZ.
Sensitivity profile of CEM/SSZ cells for DMARDs and other anti-inflammatory drugs
In clinical rheumatology, SSZ is applied sequentially in mono- and/or combination therapies with other DMARDs.19,35,20 For this reason, we investigated whether the onset of SSZ resistance affects the sensitivity for other clinically active DMARDS, as well as other drugs with potentially anti-inflammatory properties. Drug sensitivities were evaluated by their antiproliferative effects for CEM/SSZ1.5 and CEM/SSZ2.5 cells as compared with parental CEM (T) cells (table 1).
Cross resistance to mitoxantrone, a topoisomerase II inhibitor that is a prototypical substrate for ABCG2/BCRP34,36 for both CEM/SSZ1.5 (4.3-fold, p = 0.002 v CEM ) and CEM/SSZ2.5 cells (6.4-fold, p<0.001 v CEM), was studied. As expected, mitoxantrone cross resistance was fully reversed by the ABCG2/BCRP blocker Ko143. Furthermore, cross resistance of CEM/SSZ cells was noted for the DMARDs leflunomide (up to 5.1-fold for CEM/SSZ2.5, p = 0.005 v CEM) and MTX (up to 1.8-fold for CEM/SSZ2.5, p = 0.027 v CEM). Because SSZ mediates part of its anti-inflammatory effects by targeting the NFκB signalling pathway,37,38 we also determined the drug sensitivity for MG132, an inhibitor of NFκB activation through inhibition of 26S-proteasome.39 A low level of cross resistance for CEM/SSZ cells was noted for MG132 (1.6-fold, p = 0.004 for CEM/SSZ2.5 and p<0.001 for CEM/SSZ1.5 v CEM). Interestingly, enhanced sensitivity of CEM/SSZ cells was noted for the DMARDs chloroquine (up to 1.9-fold CEM/SSZ2.5, p = 0.043 v CEM) and cyclosporin A (up to 1.6-fold, p⩽0.001 for CEM/SSZ1.5 and p = 0.028 for CEM/SSZ2.5 v CEM). CEM/SSZ cells displayed even more hypersensitivity (up to 13-fold, p = 0.002 for CEM/SSZ1.5 and p = 0.003 for CEM/SSZ2.5 v CEM) to the glucocorticoid dexamethasone. These results indicate that induction of SSZ resistance can coincide with a differentially altered DMARD sensitivity pattern, including, on the one hand, cross resistance to leflunomide and MTX, but on the other, enhanced sensitivity to cyclosporin A and chloroquine, and, most notably, to dexamethasone.
Characterisation of human CEM (T) cells with acquired resistance to the DMARD SSZ showed differential expression of two MDR efflux pumps: up regulation of ABCG2/BCRP and down regulation of ABCC1/MRP1. This phenotype could be reverted (slowly) and reinduced (rapidly) after SSZ withdrawal and SSZ re-exposure, respectively. Beyond this, CEM/SSZ cells were characterised by enhanced sensitivity to the DMARDs cyclosporin A and chloroquine, and most notably to dexamethasone, which may provide possible strategies to circumvent resistance to SSZ.
SSZ is commonly used in various DMARD regimens for RA treatment, including monotherapy or combination therapy with other DMARDs such as MTX, hydroxychloroquine or in the COBRA regimen.19,20,35,40 SSZ can induce antiproliferative/apoptotic effects41 as well as anti-inflammatory effects by inhibiting activation of NFκB,37 which leads to the decreased production/secretion of proinflammatory cytokines such as TNFα.38 Although SSZ is a potent DMARD, its efficacy in long term treatment seems to be more compromised than that of other DMARDs, such as MTX.14,16,18 Because lack of efficacy may be related to either persistent/renewed disease activity and/or side effects of DMARDs, we suggested that diminished SSZ efficacy might also be associated with the development of resistance. Indeed, as previously reported,22 we found that the onset of SSZ resistance in human CEM (T) cells coincided with the induction of the MDR pump ABCG2/BCRP. Thus far, ABCG2/BCRP induction had only been noted upon development of a selected group of topoisomerase inhibitors such as mitoxantrone, doxorubicin, and topotecan.12,34,42–44
ABCG2/BCRP expression in CEM/SSZ cells did not fully account for the resistant phenotype as about 50% of the SSZ resistance was lost within one week after withdrawal of SSZ, whereas ABCG2/BCRP expression was unchanged. The nature of this latter component has not been identified, but may be related to SSZ-induced transient alterations in the NFκB signalling pathway38 that controls the transcription of anti-apoptotic and proinflammatory cytokine/chemokine genes.45–47 Consistent with this hypothesis is the observation of a two- to threefold enhancement of TNFα production/secretion by CEM/SSZ cells compared with CEM (T) cells.22 It remains to be established whether this type of SSZ resistance-induced effect may also be responsible for the altered antiproliferative effects (table 1) of NFκB signalling pathway drugs, including leflunomide,48 MG132,39 and dexamethasone.45,49,50
The gradual loss of ABCG2/BCRP expression from cell cultures of CEM/SSZ1.5 cells after 6 months' (approximately 50 passages) withdrawal of SSZ is consistent with a study by Maliepaard et al, who noted the loss of ABCG2/BCRP expression from a topotecan resistant ovarian carcinoma cell line over 30 passages in drug-free medium.51 These results indicate that ABCG2/BCRP expression gradually declines when the selective pressure is absent, but can be rapidly resumed upon renewed exposure to the selective drug.
Besides the effects on ABCG2/BCRP expression, it is of interest to note that SSZ exposure/resistance had down regulatory effects on the expression of ABCC1/MRP1. Although this MDR transporter has an established role in extrusion of various toxic drugs,2,5,11 it also has important immunological functions in, for instance, dendritic cells, where, by exporting the cysteinyl leucotriene LTC4, it mediates the signalling for chemokine CCL19 chemotaxis and migration of dendritic cells to the lymph nodes.52 Because SSZ is an inhibitor of LTC synthetase,53 impaired synthesis of LTC may parallel reduced expression of its transporter ABCC1/MRP1. Another example of ABCC1/MRP1 down/up regulation was recently identified by our laboratory after depletion/repletion of cellular folate status54 in CEM (T) cells. Consistent with the notion that SSZ can also exert antifolate effects,55 we obtained preliminary evidence that the differential expression of ABCC1/MRP1 is indeed correlated with the cellular folate status in CEM/SSZ cells (Jansen G, Scheper RJ, Dijkmans BAC, unpublished data).
The present study also provides insight into strategies that may or may not be successful to circumvent/reverse SSZ resistance. Firstly, temporary discontinuation of DMARD treatment after an initial response and resumption of the treatment at the time of progressive disease proved to be effective.56 Whether a similar strategy is also effective for patients with RA for whom DMARD treatment has failed, has not been investigated. When such a clinical strategy was mimicked in vitro—discontinuation of SSZ treatment after development of SSZ resistance and rechallenging with SSZ at the time SSZ resistance had apparently disappeared—it did not seem to be effective. SSZ resistance, along with ABCG2/BCRP overexpression, was rapidly reinduced (<2.5 weeks). Secondly, development of resistance to SSZ may be accompanied by adverse effects of collateral resistance to other DMARDs (for example, leflunomide) which might be used for sequential monotherapy. Potentially positive strategies to target SSZ resistance may include the use of (a) blockers of ABCG2/BCRP that serve as chemosensitisers to reverse SSZ resistance (for example, Ko143); (b) DMARDs whose antiproliferative activity was not impaired during development of SSZ resistance, such as cyclosporin A and chloroquine. Because chloroquine is a substrate for efflux by ABCC1/MRP1, a reduced expression of ABCC1/MRP1, as seen in CEM/SSZ cells, may confer enhanced sensitivity to chloroquine,57 which could increase the efficacy of hydroxychloroquine containing treatments.20 Finally, most interesting was the observation that CEM/SSZ cells displayed hypersensitivity (13-fold) to the glucocorticoid dexamethasone. One previous report has described collateral sensitivity to dexamethasone (10-fold) in human myeloma cells with acquired resistance to doxorubicin.58 The mechanistic basis for the markedly enhanced dexamethasone sensitivity is not clear, but is not associated with an increase in glucocorticoid receptor levels in CEM/SSZ cells compared with CEM (T) cells (not shown).
Altogether, this study shows that exposure/resistance to SSZ can have differential effects on the expression of at least two important MDR pumps: ABCG2/BCRP and ABCC1/MRP1. As these MDR pumps are normally expressed on various peripheral blood cell types,59–61 further research is warranted to identify the expression levels of these MDR pumps during treatment of patients with RA with DMARDs which include SSZ. Thus far, only a few studies have investigated blood samples of patients with RA for differential expression of the MDR transporter Pgp.62–65 Although these studies included limited numbers of patients, data were supportive for a role of Pgp in DMARD efficacy. Our present study, though based on in vitro data using a T cell model system, demonstrates also that MDR pumps other than Pgp may be relevant for DMARD resistance. Once specific MDR proteins are identified for their contributing role in DMARD (in)efficacy, this information may be exploited to use specific blockers for the various MDR pumps2 as chemosensitisers for DMARD activity.
J van der Heijden is a recipient of the 2002 Arthron Young Investigator Fellowship.
This study is supported by a grant (NR03-1-402) from the Dutch Rheumatism Association (Nationaal Reumafonds).


text:
Ordinarily I wouldn't be blogging about virtual birds. I mean, what does that have to do with renovating your world? Or the home, for that matter?
Well, the timing just seem right, given our recently announced Build a Birdhouse Giveaway Contest. So just go with it. It's actually kind of funny.
The Audubon Society just launched a social media campaign called Birding the Net. Basically they sent out a whole slew of "virtual birds" across the Internet — to over 100 different sites, including AOL, Slate and Discovery Channel, to name a few. Visitors to those sites can be on the lookout for a virtual bird swooping across the scene, perching on mastheads and nesting in birdhouses that folks can install on their personal website or blog.
The whole campaign is tied in with the release of The Big Year, the upcoming birding comedy starring Steve Martin, Jack Black and Owen Wilson.
This is a pretty cool idea. We may just have to "install" a birdhouse on our site to attract some of these virtual avian friends!


text:
Durga puja or Dussehra is one of the major festivals of Hindus. This festival is a long festival that runs for ten days. All the forms of Goddess Durga are worshipped in ten days. Goddess Durga represents the strength of women and she fights against the evils and demons and wins over them to protect mankind. The main theme of this festival is the triumph of goodness over the evils. The victory of Lord Ram over the powerful devil Ravana is also marked by the celebration of Dussehra, as Lord Ram destroyed evil and established the victory goodness.
How to share Dussehra stickers in Whatsapp?
This is a modern world where people express their emotions and sentiments with a larger number of people in leaser time. We all feel good when we are wished during the festivals. Earlier this was not possible with the people who were living at a distance. But in today's world, the distances have overtaken by the technologies. You can easily share Dussehra Stickers and GIFs with your loved ones on Whatsapp.
Happy Dussehra 2019: Stickers, Wallpapers, Images for Whatsapp & Facebook
Dussehra stickers for Whatsapp are very popular these days, as the whatsapp has come up with the new facility of sharing stickers with the people who are added in your whatsapp contacts. It can be done in very simply. Like you share emoji, you just need to select the sticker option from the drop-down menu and then choose the sticker that you want to send and then tap on the send arrow. This is how you can send stickers on Whatsapp.
Is it possible to share festival images on facebook?
Social media is a wonderful platform from where you can reach too many people at a time. Apps like facebook, twitter, Instagram are very commonly used by people all across the globe. You can easily share Dussehra images on your wall and tag people from your friend list. You can also put Dussehra wallpaper on your cover page.
Dussehra Wallpaper
Is it possible to download and share Dussehra images in Whatsapp?
Whatsapp provides you with a lot of facilities. You can easily share anything to people in just a few seconds. For sharing festival images on whatsapp you can also download the new images from the internet and share it on Whatsapp. You can simply search for Dussehra images for Whatsapp and download the picture that you like and then share it with people.
You can even put images related to festivals as your DP or profile picture both on facebook and Whatsapp. You can set Dussehra DP on every social media in a similar way. You can also share images, poems and thoughts related to the festivals with as many people as you want with the help of social media, that too free of cost. You only need to have a data connection and rest sharing doesn't cost you anything.
Different people have different ways of celebrating festivals. Some are more interested in worshipping and some people enjoy the festival season and celebrate it with their friends and families by shopping and eating. But this social media has given a new platform that connects all and so you can easily share images, stickers, GIFs, etc and celebrate the festival with everybody.
Happy Dussehra Stickers for Whatsapp & Facebook
Happy Dussehra Whatsapp Stickers


text:
VIDEO: Rosa Ree - That Gal
Tanzanian rapper, Rosa Ree closes the year with yet another major hit titled "That Gal".
Her Goddess energy oozes through this track as she defines her worth in between Dancehall influenced rap rhythms.
The official music video carries feel good energy with Rosa Ree celebrating her feminine energy alongside other beautiful women.
This track is produced by Breezy Beats while the official music video is creatively directed by Travellah.
Stream Video:
Hot stories
READ ALSO: VIDEO: Mr Blue ft. Rosa Ree - Kibao Kata


text:
This is a great article, Cheri!!! So many valuable tips, thank you!
Ten Marketing Tips for your Business or Brand
If you are in Atlanta and a UGA Alumnae, join me for a Women of UGA luncheon on Thursday, June 23, 2016 at 11:30 at Terra Terroir (3974 Peachtree Road). Cost is $30 and you can register here. We will talk marketing and I will share some tips to help you grow your business or brand.
Here are my top ten marketing tips if you can't make the luncheon …
- Have a professional pitch ready
Be able to explain what you offer in the time it would take to ride with someone on an elevator. Your elevator pitch must be clear and concise. For The Southern Coterie, our PR firm (leapfrog PR Co.) teased that it is not a 20 story building. To create your pitch, think of what words describe your brand? What are your brand's values? How do you differentiate yourself from competitors? You need three strong sentences stating your mission.
Create a Dropbox that includes your style sheet listing your fonts, colors and taglines as well as your logo saved in a few formats (vector pdf, eps, tiff and then if you have stacked and horizontal versions and even a black and white version). Be sure everyone on your team has this information and follows it. It is great to send to anyone creating marketing collaterals for you or for advertisements. Even if it is to participate on the little league t'shirt, noone wants to see their logo misshaped or in a new font.
I believe in creating a one-sheeter or media kit that includes a mission statement, brief bios of the owners, stats or prices if relevant, testimonials, photos and examples of work. You need a way to tell your story quickly and professionally over email to media inquiries or potential clients. For Bulldawg Illustrated and guide2athens, we have printed and digital versions of our media kits since sometimes we need a leave behind piece. Have high quality professional photography on hand. Top Chef Hugh Acheson once told me one of the reasons he gets featured frequently in magazines and blogs is because when they call, he has seasonal recipes with photographs prepared and ready to send. So he is efficient with his response, which means when there is an editorial hole to fill at the last minute, they remember Hugh is an easy ask and will send good content immediately.
- Create a strong website
Your website is your 24/7 sales machine. Don't ignore it. Invest in a strong design that reflects your best work. All three of our sites (www.bulldawgillustrated.com + www.guide2s.com + www.tscoterie.wpengine.com) are now on WordPress with custom features. I recommend Shopify for e-commerce as clients rave about its capabilities. Your website is your calling card. The first thing people do these days when they meet you is google you. Be sure your website makes them want to do business with you. Evaluate your google analytics so you can improve your page views and know what your visitors like most on the site. If you don't understand the analytics and SEO, then hire someone that does to help you. Insert the hand raised emoji here.
- Email marketing works
Our biggest mistake is not starting to get email addresses sooner. Get your database going immediately and start sending newsletters. Invest more time in this than social media because it is YOUR network. Set up a pop up on your website that stays up for five visits asking for visitors to sign up. Let folks know when they opt-in how often to expect emails or have different offerings so they can choose frequency so they don't feel flooded in their in-box and opt out. For Bulldawg Illustrated, we send monthly until football season and then we do one with each game. We send The Southern C on Thursdays at 6 a.m. so they start their day with us sharing entrepreneur tips and spotlights on the faces behind the brands we love. Folks that also sign up for Summit newsletters get more. Guide2athens sends monthly round ups of our blog posts about local businesses and their owners. We use Emma and they have good analytics and a blog with best practices for improving your click-thrus and open rates. For all three, we strive to use beautiful photography with well-written teasers to drive readers to click thru for more.
- Print advertising still works even in a digital age
Print advertising isn't dead. Higher levels of newspaper and magazine readership also correlate closely to higher income levels and higher education levels (reported by Nielsen Scarborough). Print readers are highly engaged with the publication. The news and features in print are viewed as more important than if shared online so they give it focused attention. It made it in print! Leverage the media in which you place the ad so be sure you select a publication that features your demographic of customer so you are establishing your brand in that readership's marketplace. Be sure your ad is memorable and for a return on investment, you must have a clear call to action. What do you want the reader to do when they see the ad? Print has a shelf life and more than one reader in a household. People put them on guestroom bedside tables and coffee tables they linger in office waiting rooms.
I recommend a mix of a print and digital buy with a media company for the best results. For guide2athens, we are selling it that way. You become a member for the year of the print edition of the book, which means inclusion in blog posts and social media support along with the two spread layout in the printed and digital guidebook and your own landing page on the website. Many publications are moving to this model of integrating their clients in all of their platforms. Leveraging the media and the brand's loyal fans in both directions. Branded content is king in print and digital if done in an authentic way and not too advertorial. Blogs have loosened print up on this topic. Even if you try to have a clear line between church and state and editorial and advertising, it's inevitable the lines get blurred and you want to support each other. Frankly, when I am looking for a resource for editorial inclusion, the people I am most familiar with their stories are my clients so naturally they land in the pages past their ad spaces.
Depending on the size of your business and your marketing budget, an analysis of other media opportunities like billboards, tv and radio is prudent. But avoid the pitfall of feeling like you have to do them all.
This is our mantra at The Southern Coterie. Find people and businesses that align with your brand and collaborate with them. If you are jewelry designer and want a shop to sell your line then start with having a trunk show there. If you create food videos then partner with a cookware line. In Athens, we often do trunk shows for local artists in shops with neighboring chefs creating the food and everyone networks and shows off their talents. If you have created a cocktail mixer then partner with a spirit brand and a food blogger to make a signature cocktail for an event at an interior designer's shop – sips and shop. Strength in numbers! Do giveaways with brands that have similar customers to yours. Offer your services for free the first time to forge a relationship. Feature each other on your blogs and social media. One of my clients, The Vine, has created an advisory board of business people they respect. It has be an invaluable resource for their growth.
{Collaboration with Schermer Pecans + Sea Island Forge – Photo: Lilly Jo Photography}
I will dedicate five of the ten tips to social media because it is a necessity in marketing your brand or business in 2016 and here is why …
BY THE NUMBERS provided by Waiting on Martha
- Social Media influences 93% of the buying decisions of online shoppers
- 5 BILLION Facebook likes are generated daily
- 60% of all the social media traffic on business websites come from Facebook & Twitter
- There are 77 million Instagram users currently and by 2018, one in every three people will have an account
- 88% of people have purchased a product they pinned on Pinterest
- 51% of people say Twitter influenced their consideration when making a travel decision
- Snapchat has 100 million monthly users and growing
- Twitter followers are 72% more likely to make a future purchase from that brand
- Social media is a conversation with your customers
A conversation means it should be a two-sided exchange. Validate others ideas. Respond to all comments on posts promptly. Follow your clients and comment on their posts. Share others photos and posts but always tag and give credit. This will grow your reach organically and increase brand loyalty, which converts to sales.
- Participate in the social media where your customers are
Don't join every social media and fragment your time and efforts. Do the research and choose the platforms where your customers spend the most time and do a jam up job there. If customers visit your feed and you haven't posted in six weeks or even six days, then they won't return so if you join a platform then you must be consistent and post regularly.
- Speak the correct language on each platform
Each platform requires a different language and serves a different purpose so participate wisely.
Facebook for all three of my companies is the highest referral to links to our website's posts. For us, the goal is get them on our site reading our content and engaging with our sponsors. Facebook might be my least favorite but it is the most effective for driving traffic to our site and therefore a necessity. These days the way the algorithm works, you can't post too much. And the demographic skews older but my UGA interns still use it even if they prefer snapchat. Facebook has so many bells and whistles so be sure to utilize their facebook ads for boosting posts, increasing conversions on your website, raising attendance to your events and they can zero in laser focused to your demographic you desire. Link your newsletter sign up on your page, utilize their analytics to understand your followers better and if you have a spotify shop then set up their free shop app.
Twitter is fabulous for headlines about current events for our media company and I mean current as sometimes you hear it on twitter before it can make the 24-hour tv news! It's a great quick way to connect with your followers. We share links and it is a good driver to our sites too since folks are on their mobiles and happy to click a bit.ly link over for a read. We get conversations going by sharing photos or statements about local happenings (guide2athens) or sports updates (Bulldawg Illustrated) and it's great during the Summit to share quotes from presenters or photos of sponsors and their pretty set ups (The Southern Coterie).
Instagram is the highlight reel! It's my personal favorite but I am a visual person and love pretty photography. Quality photography is imperative. My husband Vance will send me a photo for instagram and I will politely tell him that it is going to be great on twitter. People are likely following national magazines and brands so to share a photo of poor quality in their feed will stand out and get an unfollow. We do two posts a day (a.m. and p.m. so you start and end your day with us) on all three of our accounts and we just started using Planoly to organize our feeds. This lets us work as a team to decide what posts look good in what order – you should always evaluate your feed in its quilt of nine photos and be sure it is consistent and flows with some up close detail shots and some blue sky further out shots and colors mixing well. Be sure to have enough negative space throughout the feed.
Snapchat is the behind the scenes and more candid and less edited. I advised a shop recently to show boxes getting unpacked with new merchandise, styling a display, creating an outfit of the day for an instagram pic #OOTD. Let them get to know the staff and brands in a natural way but keep it professional or it is a liability not an asset.
Pinterest is so great for aspirational sharing and folks looking for something. It's a great place to share entertaining ideas, recipes, DIY, fashion and interiors. Keyword rich descriptions help with search. Organize your boards well and you have the option to add a category to your board, which will help your pins receive more exposure on pinterest. Pinterest awards you more exposure the more you pin but don't pin all at once and flood the feed – schedule posts. Create and contribute to guest boards for more exposure. Apply for rich pins. Vertical images and photos with multiple dominant colors (red and orange outperform blue) get re-pinned the most. I create blog boards for my topics and pin all my posts there so I have a Georgia Girls board with all my Q&As with Women of UGA there and sometimes I promote the board so they can browse the whole line up of interesting UGA graduates. I do boards on pinterest for The Southern ( C)ity Guides and have Coterie members in the towns contribute to them and share their favorite spots in the cities. I have been negligent on this platform and after Mandy Rye's session at the Summit, I am renewing my efforts. We have signed up for Tailwind, a scheduling app for pinterest that gives good analytics so you know what is working.
Periscope is a twitter platform. Much like twitter, it is very current. People join in live while you are showing them something. We have used it to let people have access to something they are not attending. For instance sometimes we periscope the halftime show at a Georgia game or a coach speaking at an alumni gathering. We have periscoped a food truck festival in Athens for guide2 and asked cooks and attendees to share about the offerings. For the Summit, Mandy Rye of Waiting on Martha periscoped her session and we took questions via twitter and periscope and our audience for that became so much bigger than the ballroom where she presented.
{Mandy Rye of Waiting on Martha presenting at Summit – Photo: Kathryn McCrary}
- Grow your audience organically
Don't worry about the numbers and definitely don't buy followers. It will be obvious, as your engagement won't match up and people won't trust you. And it's the comments and likes that are more likely to equate to conversion to a purchase. You want your followers to truly be interested in you and what you offer. Quality followers over quantity.
- Use one social media to promote the other
Be sure to share what is going on over at your other social media. Use them to drive traffic to each other. Share your pinterest board as a link on facebook. Tweet that you are periscoping live. Share a photo on instagram and say for the behind the scenes of this outfit, watch me style it on snapchat.
- Carefully use your social media like an advertisement
For Bulldawg Illustrated, we do a lot of videos interviewing the players on our youtube channel and we have sportscasters and writers join us for podcasts on our Soundcloud channel. We share links to all of this on social just like we share links to our blog posts. Our advertisers are floating run of site and in our digital issues and they are a priority. Our intent is to have great content and great sponsors that we present and they want to support. On The Southern C, we promote our sponsors and attendees by sharing their news and successes. Guide2athens is a curated collection of Athen's best businesses and we spotlight them on our feeds. We try our best to do it all in an entertaining way and not too advertorial but let's face it, we aren't spending all this time on social media purely for the fun of it. The point is to engage potential customers and convert them to sales. I can't tell you how many times folks have said to me I drooled over the guide2athens picture of Mama's Boy big pimento cheese biscuit and drove over and ate there that day. SCORE!
{Home Page Photo of Emily Ley Brainstorm Books for Summit – Photo: Lilly Jo Photography}
FOR RECENT POSTS BY CHERI LEAVY – click here


text:
Two months after launching in beta on iOS and Android, Microsoft Edge has dropped its preview tag and is now available for everyone on both mobile platforms. Although the Android version of Microsoft's web browser was generally available on the Google Play Store, that wasn't the case for the iOS version which was initially released through Apple's Testflight program.
If Microsoft Edge is already your main browser on your Windows PC, then you can now enjoy a continuous browsing experience across your mobile devices, with seamless content and data sync. Microsoft's mobile browser also includes handy features such as a QR code reader, voice search and a convenient Hub view to quickly see all your favourites, reading list, history and books all in one place.
If you can set Microsoft Edge as your default web browser on an Android device, it's still not possible to do that on an iPhone. Moreover, the iOS app doesn't have an iPad layout for now. But overall, Microsoft Edge is a pretty solid browser on both mobile platforms and it's a must-have if you frequently use the web browser on Windows 10. You can check out Microsoft Edge on your iOS and Android device with the download links below.


text:
'Profoundly concerned' over violence in Libya, Security Council warns of possible sanctions
In a press statement issued this morning, the Council, recalling resolution 2174 – which it adopted in August and condemns the use of violence against civilians and civilian institutions – emphasized that the Sanctions Committee is prepared to sanction "those who threaten Libya's peace, stability or security or that obstruct or undermine the successful completion of its political transition."
Reaffirming its strong commitment to the "sovereignty, independence, territorial integrity and national unity" of Libya, the Council also underlined that there can be no military solution to the current crisis.
Echoing a statement yesterday from the Secretary-General Ban Ki-moon, the Council also strongly condemned the escalation in violence and noted with concern the recent attacks on public and civilian infrastructure.
Expressing full support to Bernardino León, Special Representative of the Secretary-General and Head of the UN Support Mission in Libya (UNSMIL), the Council urged all parties to "engage constructively with his efforts to resume an inclusive political process aimed at addressing the political and security challenges facing the country."
In addition, the Council strongly condemned ongoing human rights violations and abuses in the country, as well as the use of violence against civilians and civilian institutions, and of public intimidation, including of UN personnel.
It also condemned attempts to intimidate and obstruct the proper functioning of Libya's financial institutions.
Yesterday, Secretary-General Ban Ki-moon voiced deep concern over the uptick in violence across Libya and urged all parties to recommit to the values of the revolution that inspired the North African country's break towards democracy.
Since the 2011 uprising that ousted former leader Muammar al-Qadhafi, violence among armed groups has spread throughout the North African country, causing a humanitarian crisis.
According to numbers provided by the UN refugee agency (UNHCR), a total of 393,400 people have been displaced since May.
Earlier in the summer, there seemed to be steps in the right direction with the election on 25 June of a national Parliament, a move UNSMIL hoped would thrust Libya towards political resolution. However, earlier this month, Libya's Supreme Court declared the national Parliament unconstitutional.