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Coming Attractions, Fast and Furious? | Other Orlando
If you are like me, you may have read about the possibility of a "Fast and Furious" ride coming to Universal Orlando Resort. Only a long-standing rumor, sure, but the possibility brought up the question in your mind as well as mine: what else can theme park goers expect in the future?
Now, this is no immediate gratification because we will have to wait.
But really not for long.
That's because SeaWorld Orlando is set to make its biggest splash yet.
For those who can't or don't want to wait, there's also Mako -- due to open any time. It is said to give SeaWorld Orlando its biggest splash yet. Why?
It is the tallest, fastest and longest roller coaster here. Named for a fast-moving shark, Mako almost flies with speeds up to 73 miles per hour, the attraction says. And it is a fast-moving experience like a predator swimming speedily through the water at top speed chasing dinner.
"It will be a wild mix of fear, thrills and fun," predicts Brian Morrow, SeaWorld's attraction creative director.
But what's next? And when?
This is a subject that theme parks prefer to tell you themselves. But speculation, often based on part performances, is normal.
The biggest possible future attractions are associated with "Nintendo, Star Wars and Avatar."
A quick look back at 2014 shows that it was an extremely active one.
Consider what opened: "Diagon Alley," the second Harry Potter land at Universal Orlando, a slew of roller coasters, including the "Seven Dwarfs Mine Train at the Magic Kingdom," and others. They made it a vintage year for roller coasters and new rides. This year has not seen that type of activity or record-breaking rides generating huge lines.
Theme park experts attribute the success of attractions like Harry Potter's at Universal as spurs to push parks trying to up the ante and compete with Disney. Meanwhile, competition everywhere for theme park-goers should continue to draw a lot of speculation, but also obviously add up to many new attractions
There are a lot of minor but possibly significant new rides and activities planned soon.
Another Starbucks, for example, is coming to Disney's Animal Kingdom (apparently proving that visitors to that particular park like their coffee). And while this may be good news for the caffeine-starved, it has limited appeal to many other visitors.
So for purposes of what you read here, we will try to confine this report to major areas.
Kong will be back
One of these you probably already know.
We already know, for example, that more than a decade after "Kongfrontation" closed, the big ape is coming back. "Skull Island: Reign of Kong" is scheduled to open in the summer of next year at Islands of Adventure.
It's inevitable that will be a "multi-sensory, multi-dimensional experience."
It will also take ride-goers back to the 1930s, when the film first came out. Universal consulted with Peter Jackson, director of the 2005 remake of the 1933 movie, for suggestions on the new ride.
It will be a major attraction, of course.
This will be the second King Kong attraction at Universal Orlando. The first, "Kongfrontation," one of the original rides at Universal Studios, was closed in 2002 to make room for "Revenge of the Mummy." There have also been two "King Kong" attractions at Universal Studios in Hollywood. All have been different.
The Skull Island ride "is not a story line from any movie or attraction. It's next generation," a spokesman said.
The ape breaks out of The Big Apple
This time, the ape won't be wreaking havoc on New York.
"The fact you're there in his home instead of him coming to your home is what sets this attraction apart," said the spokesman.
Ride-goers will walk through the jungle and the ruins of a temple, then board an expedition truck for Skull Island. Here, they will encounter a lot of hazards, hostile natives, and some so-far unnamed terrors. The final one of these is Kong himself.
Now we come to rides that are no longer exactly in the rumor category:
Nintendo. Yes, it's coming to Universal.
The companies had this to say in a joint statement:
"Universal theme parks offer incredibly popular, innovative themed family entertainment experiences based on compelling stories and characters – using powerful storytelling and innovative technology, Nintendo has created remarkable and imaginative worlds filled with captivating stories and beloved characters. Now, for the first time, those stories and characters will be brought to life in entirely new ways – only at Universal theme parks."
When and exactly what are still speculation. More details are expected later, of course.
New territory for theme parks
But at least one newspaper account termed this "entering new territory" for theme parks. The idea conjures up life-size Mario Karts and Splatoon water parks.
Universal Orlando has created haunted houses based on video games "Resident Evil" and "Silent Hill" for its Halloween Horror Nights events. But in general, theme parks are "very, very new to the concept of gaming," said Susan Arendt, managing editor of GamesRadar+.
Not entirely new, however.
Rosen College of Hospitality Management associate professor Duncan Dickson pointed to the success of Disney's "Wreck It Ralph," an animated comedy that revolves around a video-game character, in 2012.
Star Wars: the reality
Another attraction with few details that seems inevitable in part because it is heard about so often: Star Wars. The trade publication "Variety" called the Star Wars franchise a continuing "big tease." No wonder.
When Disney announced a strong financial results earlier this year, head Bob Iger told Wall Street analysts that the presence of the film characters were becoming a force. He said the company Imagineers were looking at many locations around the world.
Specific plans would be announced later this year, he said.
"Fairly soon, I'm sure we'll be ready to go public with some specifics. But it's safe to say that you'll see a lot more 'Star Wars' at Disney and at Disney parks in the near future," Iger said.
His future announcement may very well coincide with the new release of the latest film "The Force Awakens" in December.
Disney has has an obvious uptick in attendance after the introduction of new rides and themed lands designed around its popular film properties. So films understandably remain as popular ride themes.
Disney already is building an "Avatar"-themed land at its Animal Kingdom Park in Orlando. That land is set to open in 2017.
Ride the flying banshees
Avatar land will feature Pandora's floating mountains, plants that glow in the dark and a boat ride through the jungle. But its star attraction will be a ride on flying banshees like the ones that the Na'vi ride in the movie.
Disney President Bob Iger rode recently on the back of a flying banshee. Not surprisingly, he reported in Variety that it was "so real, so lifelike…There's never been anything like it."
Rides are described as "banshees brought to life" via large video screens. The rides promise 3-D action inside a huge movie theatre. The attraction is said to include Pandora's floating mountains and various huge plants that include restaurants, of course.
The themed addition, designed with film director James Cameron, represents the largest expansion to Animal Kingdom since the park opened in 1998, according to newspaper reports.
Another potentially very popular ride is from the hit movie "Frozen."
It is being built in the space in the Norway pavilion that had been occupied by Maelstrom, a boat tour of Norway's cultural and geographic highlights. It is scheduled to open at Epcot in the first half of 2016. Because the ride will open relatively quickly — less than two years after Maelstrom closed — theme park experts say the new ride probably will be built on the same track as Maelstrom rather than starting from scratch. Disney is also building a separate meet-and-greet space nearby for Frozen's heroines, Anna and Elsa, but has not said when it will open.
Other upcoming attractions:
At Disney, "Rivers of Light" is described as a nighttime show that is a combination of live music, floating lanterns, water screens and animal imagery. It is due to open next year on the Discovery River in front of Expedition Everest at Animal Kingdom.
In nearby Legoland, a new attraction is now open: Heartlake City, based on the Lego Friends toy line The new area is based on friends Andrea, Emma, Mia, Olivia and Stephanie in a toy line introduced in 2002. It will have a horse-themed roller coaster called Mia's Riding Adventure, the interactive Friends to the Rescue show, and new shops in Heartlake Mall.
Busch Gardens Tampa announced plans for a new family thrill ride called "Cobra's Curse," opening next year. "This spin coaster will be the only one of its kind in the world, featuring a vertical lift and taking riders on a whirlwind adventure of exciting explorations," says a news release from the theme park about 90 miles from Disney. Key features of the ride will include an 80-foot snake icon, a trek over the park's Serengeti Plain and displays of an Egyptian archaeological excavation.
Already underway and previously mentioned are Universal Resort's plans for Volcano Bay, a themed water park within the resort set to open in 2017.
Fast moves?
As for "Fast and Furious," speculation was raised during the opening of Universal Studios Hollywood's hosting the new "Fast & Furious: Supercharged" attraction in late June. During a talk with media, actress Michelle Rodriguez discussed her excitement about the ride and the potential of it moving to other parks. "So I'm wondering if this thing is going to travel, if it's going to go to Florida and then maybe China," she said at a news conference.
No ride confirmation, of course, but the possibility of another movie attraction is a long-running rumor. Even if it does not happen, it shows that rumors of new rides are not limited to the general public. They are also of interest even to movie stars who are in the shows that may end up as theme park rides.
Coming Attractions, Fast and Furious?

redpajama_set_name: RedPajamaCommonCrawl


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«Раскол» и «Отбой» — два варианта издания одной записи концерта рок-группы Nautilus Pompilius, прошедшего в ГЦКЗ «Россия» г. Москвы 4 августа 1988 года и изданного в апреле 1994-го. Этот концерт был одним из последних в данном составе: 10 ноября Вячеслав Бутусов впервые распускает группу.

Разница возникла в результате того, что альбомы сводили разные звукорежиссёры (см. Участники).

Фактически «Раскол» стал номерным альбомом, многих его композиций не существует в студийных версиях, а при подготовке издания звукорежиссёр убрал аплодисменты зрительного зала, приблизив тем самым звучание к студийному.

На обложке виниловой пластинки «Отбоя» изображён профиль Вячеслава в виде топографического образования, «мальчик-лето» с лицевой, и «мальчик-зима» с оборотной стороны конверта.
Всего Nautilus Pompilius дали в начале августа 1988 года три записанных концерта в ГЦКЗ «Россия». Помимо «Отбоя» были сделаны ещё и две видеоверсии концертов записанные 1 августа 1988 г. (неофицальное название «Яблоки») и 3 августа под названием «Nautilus Pompilius Live». Также в интернете есть две видеозаписи с того концерта, это песни «Хлоп-хлоп» и «Мой брат Каин».

Производство
Параллельно с ростом популярности группы к 1988 году в ней начали возникать творческие разногласия: большое количество концертов, коммерческий успех, неблагоприятная обстановка в советском рок-сообществе негативно сказывались на отношениях внутри группы. Дмитрий Умецкий считал, что коллективу необходимо прекратить концертную деятельность, сосредоточившись на создании творческих идей и потенциала, однако его предложение не нашло поддержки среди остальных музыкантов. В начале февраля бас-гитарист предъявил ультиматум: если группа не прекратит концертную деятельность и не переедет в Москву, то он выйдет из состава. Несмотря на его заявление, остальные музыканты проголосовали за продолжение проведения концертов, и в результате Умецкий покинул «Наутилус». Вместо ушедшего Дмитрия Умецкого на бас-гитаре стал играть Виктор Алавацкий — бывший коллега Алексея Хоменко по группе «Слайды».

Для проведения концерта в Химках в качестве бас-гитариста был временно вызван звукорежиссёр Владимир Елизаров.

По приглашению лидера «Наутилуса» в июне появился Егор Белкин, который участвовал в коллективе вплоть до его первого распада. Другие музыканты сначала не были согласны с таким решением по включению в состав Егора Белкина. Убедить их Бутусов сумел тогда, когда он объявил, что сам выйдет из «НП». Однако это никак не сказалось на улучшении отношений среди членов «Наутилуса».

Для того, чтобы не было необходимости прекращать гастрольную деятельность, летом 1988 года «НП» записывает концертный альбом «Раскол» («Отбой»). В него вошли песни, созданные после выхода «Разлуки» (1986), и которые по той или иной причине не вошли в «Князя Тишины» (записан в феврале-марте 1988 г., издан в 1989 г.). Студия «Sintez Records», возглавляемая Александром Кутиковым, записала выступление группы на многоканальный магнитофон, но звукооператор Владимир Елизаров остался недоволен сведением. В результате вышло две версии альбома, сведенные Елизаровым и Кутиковым .

Список композиций
Авторы всех песен — Вячеслав Бутусов (музыка) и Илья Кормильцев (тексты), кроме указанного особо

Версия «Раскол»
 Синоптики (слова — Вячеслав Бутусов) — 4:39
 Мальчик Зима (слова — Дмитрий Умецкий) — 2:21
 Бриллиантовые дороги — 5:16
 Город братской любви — 4:07
 Падал тёплый снег — 3:08
 Чужой (слова — Вячеслав Бутусов) — 6:16
 Ворота, откуда я вышел — 3:35
 Мой брат Каин — 4:15
 Отход на Север (слова — Вячеслав Бутусов) — 3:42
 Новые легионы (Песня в защиту женщин) (слова — Вячеслав Бутусов) — 3:16
 Bonus track — 8:31
 Переиздавался без бонус-трека в рамках серии «Архив» (DANA Music, 1997)

Версия «Отбой»

 Синоптики (слова — Вячеслав Бутусов)  — 4:50
 Мальчик-Зима (слова — Дмитрий Умецкий) — 2:24
 Город братской любви — 4:12
 Новые легионы (слова — Вячеслав Бутусов) — 3:12
 Падал тёплый снег — 3:09
 Ворота, откуда я вышел — 3:44
 Чужой (слова — Вячеслав Бутусов) — 6:05
 Отход на Север (слова — Вячеслав Бутусов) — 3:45
 Мой брат Каин — 4:18
 Бриллиантовые дороги — 5:29

О композициях
На обоих вариантах представлены песни, исполнявшиеся в концертном туре «Наутилуса» 1988 года и не выпущенные на студийных дисках группы — (1), (2), (6), (7), (8). Композиции (4), (5), (9), (10) были позже записаны в студии в новых аранжировках и выпущены на альбоме «Наугад» в 1990 году.

Участники
 Вячеслав Бутусов — вокал, гитара
 Алексей Могилевский — клавишные, саксофон, бэк-вокал
 Виктор «Пифа» Комаров, Алексей Хоменко — клавишные
 Егор Белкин — гитара
 Виктор Алавацкий — бас
 Владимир «Зема» Назимов — ударные
 Звукорежиссура, сведение версии «Раскол»: Владимир Елизаров.
Версия «Отбой»:

 Звукорежиссура: Александр Кутиков
 Сведение: Александр Кутиков, Владимир Елизаров.

Приём
Во время проходивших в августе 1988 года концертов в ГЦКЗ «Россия» многие поклонники начали уходить из зала.

Альбом «Отбой» Находился в первой тройке хит-парадов осени 1994 года.

Примечания

Ссылки
 Информация об изданиях альбома «Раскол», изображения обложек

Альбомы группы «Наутилус Помпилиус»
Концертные альбомы группы «Наутилус Помпилиус»
Концертные альбомы 1994 года
Альбомы Sintez Records
Альбомы Jeff Records

redpajama_set_name: RedPajamaWikipedia


FINLAND: Helsinki metro operator HKL announced last month that the contract for Siemens to automate the city's metro line could not be fulfilled due to cost and technical factors.
Following two days of discussions, the scope has been scaled back and Siemens has offered a discount on the €100m deal signed in December 2008. Automated running on the 21 km line is still envisaged in 2014, but with a driver on board to control the doors and other functions.
A key stumbling block was the need to retrofit equipment on the 42 two-car M100 series trainsets which date from 1977-84 and following modernisation in 2004-09 are expected to last for another 20 years; the 12 Alstom M200 sets do not face the same problems. A further concern was the timetable for completing the 14 km western extension of the metro to Espoo.
An extension of Helsinki tram Line 8 from Salmisaari to Jätkäsaari opened on January 1, serving the former cargo harbour area at Jätkäsaari which is being redeveloped as a mixed commercial and residential suburb.
Planned by WSP Finland and built by VR Track and Rataratkaisut at a total cost of €2·3m, the 1·9 km extension has three stops. The extension includes the separately-funded Crusell Bridge built by Skanska Infra, which provides tram and road access to a district which was previously served only by a single road.


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Home Sports Broncos opening round playoff schedule announced
Broncos opening round playoff schedule announced
By Steven Mah -
The Swift Current Broncos loss in Regina Wednesday locked them into third spot in the East Division, clinching home-ice advantage for the Moose Jaw Warriors for the opening round of the Western Hockey League playoffs.
The Western Hockey League released the best-of-seven series schedule shortly thereafter, with the first two games to be played in Moose Jaw next Friday and Saturday. The series will shift back to Swift Current on March 28-29 for games three and four. Game five would be March 31 back in Moose Jaw. Game six is slated for April 1 back in Swift Current. A seventh and deciding game, if necessary, would be played April 3 in Moose Jaw.
The two teams will conclude the regular season against one another this weekend, beginning Friday in Swift Current and then Saturday in Moose Jaw. The Warriors have won three of the four games so far in the series season.
1 Swift Current @ Moose Jaw Friday, March 24, 7 p.m.
2 Swift Current @ Moose Jaw Saturday, March 25, 7 p.m.
3 Moose Jaw @ Swift Current Tuesday, March 28, 7 p.m.
4 Moose Jaw @ Swift Current Wednesday, March 29, 7 p.m.
5 * Swift Current @ Moose Jaw Friday, March 31, 7 p.m.
6 * Moose Jaw @ Swift Current Saturday, April 1, 7 p.m.
7 * Swift Current @ Moose Jaw Monday, April 3, 7 p.m.
Previous articleBroncos fall again to Pats
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Steven Mah
Steven Mah is a Sports Reporter at the Swift Current Southwest Booster. See news happening? You can reach Steven at 306-773-9321 or boostersports@swbooster.com or on Twitter @swbooster.
U13 AA Wildcats win twice in Weyburn
Schafer wins Viterra Saskatchewan Scotties
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Steven Mah - January 31, 2023


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Home » News » Defining a billing strategy
Defining a billing strategy
Posted on Wednesday, August 4, 2021 - 12:52
The big intent of leading channel billing providers is to create a dynamically driven balance between their software R&D and the demands of a fast evolving market.
Only then, they say, can resellers ensure that their strategic plans will deliver growth and contribute to long-term sustainability.
This month's expert panel is clear that the provision of appropriate billing software and services is fundamental to the success of reseller growth strategies. And according to Inform Billing Managing Director Shaun Bodsworth, the contraction of traditional services has opened the floodgates for resellers to deliver new sources of value. "We are seeing paradigm shifts in business fundamentals and the channel reinventing itself to adapt to the opportunity," he stated. "The possibilities for wider streams of revenue generation from each customer are there for the taking – and a billing platform enables the delivery of monetisation opportunities. Cloud technology facilitates the addition of new services and products – but the strategy needs to be thought through first."
Moving forward with strategic confidence goes hand in hand with analysing past trends, noted Bodsworth. He says reseller growth strategies work best when based on billing reporting analysis, practiced and assimilated as an integral part of the overall plan, not merely an initiative. "Predicting future scenarios and acting on them involves close assessment of billing intelligence to determine potential risks and identify the drivers for new opportunities by tracking customer behaviour," he said. "This needs to be a continuous process until it becomes part of the culture across the entire business."
Laying your hands on meaningful analytics requires an investment in time, people and systems, as well as an understanding of where to get the most insightful data and the tools to consolidate the information. But the rewards are worth the investment in time and money. "By pulling data together you can see the overall picture and truly understand the customer and how they like to be served and supported," added Bodsworth. "The opportunity is there to easily deploy new products, services and pricing bundles to boost revenues and market share."
As well as data analytics, cloud-based billing software provides an opportunity for revenue monetisation. No longer hampered by time and resource consuming manual processes, resellers can be more creative and deliver proactive solutions, rather than react to change. That's not all. "The value of digital transformation offered by cloud-based billing makes the supply chain more efficient, agile and customer-focused," added Bodsworth. "It brings down the walls between silos and becomes a completely integrated ecosystem that is fully transparent. It enables resellers to react quickly and even anticipate scenarios, therefore implement real-time change as well as achieve earlier revenue collection. Manual systems that create inaccurate billing for the complex scenarios can be a thing of the past, with automated systems delivering through clever APIs."
The possibilities for wider streams of revenue generation from each customer are there for the taking – and a billing platform enables the delivery of monetisation opportunities
Inform Billing invests over 45 per cent of revenues into increasing its software capabilities, mainly around business intelligence data, monetisation through product and service offerings, or increasing self-serve capabilities. A current priority is the development of API and integration capabilities to deliver more streamlined processes, not just for isolated billing strategies but the wider reseller business. "A key part of our service is to make the billing data and reporting capability as easily available as possible," commented Bodsworth. "Moving forward, resellers need access to integration tools to consolidate their data into a data warehouse or an analytics programme."
More powerful, flexible and accurate billing and analysis capabilities are now essential for success in the evolving commercial landscape, reiterated Simon Adams, Managing Director, PRD Intelligent Billing. "This is especially the case for businesses that need to rapidly scale their customer base and adapt fluidly," he said. "A wider and more flexible monetisation strategy is required, along with systems and software capable of accurately processing, analysing and billing the data for increasingly complex and integrated revenue streams."
Against this backdrop of unprecedented industry change – not to mention Covid-19 factors - all service providers are continually having to review, adapt and redefine their monetisation strategies in line with the need to diversify and expand their offerings across the channel. "To be successful, businesses require billing platforms that can flex with them, providing accurate, real-time reporting capabilities and data analysis," added Adams. "Accurate data analysis and reporting is crucial to ensuring opportunities and monetisation strategies are optimised to maximise revenue potential."
Intelligent Billing covers multiple market sectors and data streams with options to converge all invoicing into a single monthly or ad-hoc bill and reports, all of which can be tailored to the end customer. "Accurate, real-time billing and reporting capabilities provides resellers with the data and analytics to assess end customer performance and value," said Adams. "This enables them to quickly identify which services and offerings are performing or may need additional resources and investment to maximise opportunities. Resellers can quickly modify their business model accordingly."
Accurate data analysis and reporting is crucial to ensuring opportunities and monetisation strategies are optimised
Integration with other key business systems, such as accounting software, combines data from multiple sources to produce tailored intuitive reports that support strategy planning, noted Adams. "Seamless API integrations into third party best-of-breed software systems is essential," he added. "We will be investing in the continued development of our API capabilities and new innovations in this area. We also aim to automate wherever possible to simplify the billing and analysis process. The ongoing evolution of billing systems enables resellers to offer flexible, tailored packages and bundles to customers."
Automation is also key to success – but only if data is fully harnessed, concurs Tekton Billing Director Harry McKeever, who cited an adage – if you're not assessing, you're guessing. "Telecoms billing is awash with data, from which valuable insights can be learnt, but the right platform is required to translate and visualise that data into actionable insights," he said. "Some platforms are guilty of dumping reams of raw data, giving the illusion that there's easy access to lots of information. But in reality, raw data tells us very little, and even if you're exporting data and manipulating it in an external system like Excel, then you're wasting precious time on a platform that's not working for you. Visualisation and comprehension, rather than raw data, is key."
Resellers can truly enhance their operations, but only if the data leads them to the following discoveries, pointed out McKeever – from identifying upsell opportunities for customers reaching or breaching bundle consumption; the refinement of wholesale shared bundle allocations; identifying subtle customer churn characteristics before it's too late; spotting carrier billing inaccuracies and assuring revenues (and more). "These days, it's also more common to expect regular fluctuations in monthly billing as end users add and remove users from their subscriptions," added McKeever. "And with the increased volume of subscription provisioning it's plausible that mistakes can happen and billing will be forgotten. So, the ability to reconcile imported supplier subscription charges is paramount.
"It's critical that a billing system can handle these mid-month quantity changes elegantly and accurately. Having to cease a service charge and restart a new one can often be clumsy, error prone and offers little in the way of continuity of reporting. And a good billing system allows for date driven amends to charges, without having to treat it as a separate charge altogether. Meaning more accurate billing and less chance of a frustrated call from an end user with bill shock."
Telecoms billing is awash with data from which valuable insights can be learnt, but the right platform is required to translate and visualise that data into actionable insights
Traditional services are all too often similar to products sold by the competition, so resellers are advised to differentiate through other outlets such as value adds and inventive commercials, pointed out McKeever. "Billing vendors will typically advise that it's best practice to keep any pricing standard and uniform," he added. "In a perfect world we'd agree. But sadly, it's often deficiencies in the billing system that lead to this recommendation. Plus, in the real world, bespoke pricing is unavoidable! However, Tekton believes that resellers shouldn't be limited by their billing platform, and bespoke pricing needn't be a taboo subject."
Billing is, arguably, the most regular touchpoint resellers have with their partners, and the right billing solution and portal will give that all important sticky factor rather than being regarded as just a back office tool. "Businesses can only grow efficiently after they address customer churn," stated McKeever. "That's why much of Tekton's efforts have been focused on developing a strong customer portal."
And within the overall objective of delivering value to customers, we can see that momentum towards the key themes of analytics, the cloud, integration and more streamlined processes must be achieved. Onecom's acquisition of 9 in March brings a wider capability in these areas through an extended team of development experts as well as new technologies and resources, focusing on integration capabilities, speed, insight and increased intelligence, all cited as areas for innovation by Nick Jarrett, Head of Revenue Management & Billing at 9 Group. "This ensures that billing systems are open and transparent, so that data can be read and interpreted and customer led change can be implemented swiftly," he said.
"Analysing and understanding your billing data is absolutely critical to maintaining a profitable customer base. By using billing software to monitor data trends, you can stay a step ahead and adjust your offering to help protect and grow margins. Customer behaviours are constantly evolving and the pandemic has accelerated change in a way that we could never have predicted. Businesses across the board are under pressure to understand and respond, and there is pressure to diversify revenue streams to protect and grow margins."
Partners should look to their service provider for a more human level of support beyond the processing and production of customers' bills
Billing systems are designed to identify and map changes around customer behaviour and usage. Shrewd partners will lean on this for regular commercial intelligence, rather than simply using their billing software as a mechanism to issue invoices. "By using billing software to monitor change, proactive partners have reshaped their commercials to fit with the current climate," said Jarrett.
From the customers' perspective, the role of billing software is to manage the seamless presentation of complex billing data. They want a single bill which arrives on time and is clear and accurate. "But billing needs to be so much more than simply a processing function," added Jarrett. "There is an opportunity for service providers to deliver a real value add by supporting partners and their customers with the entire managed billing and support wrap."
"The human element of billing should never be overlooked. Partners should look to their service provider for a more human level of support beyond the processing and production of their customers' bills. This can include follow up support, the management of customer billing queries, commercial insight and helping partners to make sense of their billing data."
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We had the most wonderful time at our Stamping to Share Fall Flair 2017! I almost can't believe that it's over already. The last two weeks of prep and preparation have been so much fun. We did capture a few memories and the video that I am sharing with you today will show you how we created some of our Halloween Giftables.
At 7:30am, we had our set up crew arrive and set everything up. Pictured above from left to right: Sharon Merritt, Mychelle Rossberg, Kim Lundstrom, Stacey Krats, Julie Johansen, Linda Emery, Pam Salinas, Dorene Bye, Mary Alice Bellis and myself.
I am so incredibly grateful to members of my Stamping to Share group who make Fall Flair and Spring Fling possible. TOGETHER we make quite the team as you will see by the pictures below! We are also extremely grateful to all the customers who sign up to attend these events. Their praise and gratitude spurs us on as we take a small break and then begin the planning process for Spring Fling 2018!!
The project bags turned out so cute. My niece, Molly, prepared them for us. She loves to do it and does a great job! The how to is on my video today.
These are all the decorated Mini Pizza Boxes prepared by Mychelle Rossberg. They held our customer product gifts. I share all the how to's and show you what's inside the box in my video today.
Dorene Bye and friends created these cute treat holders with the Clear Tiny Treat Boxes. We filled them with chocolates for an After Lunch Chocolate Trick or Treat. They were adorable and they are also featured in my video today.
Kim Lundstrom designed and created all 115 name tags! They were just adorable!! The sparkly collars were created with the Mini Black Sequin Trim.
Everyone seemed to be having a great time making all the cards. Most of the cards were designed to feature products in our Stampin' Up! 2017 Holiday Catalog.
This is one of my downline, Tammy Nelson, who came up for the day to make cards with us. She recently earned her first Incentive Trip with Stampin' Up! and will be on the Alaskan Cruise in 2018!
And another fun picture of some of our demonstrators and guests at Stamping to Share Fall Flair 2017. Enjoy the How To Video!
24/7 Shopping at my Stamping to Share Website Who doesn't like to shop in their jammies? Did you know that every person who places an online order with me receives a hand stamped card in the mail? AND, if you use the current host code and purchase at least $25, you will receive a "Paper Perk!" The current Host Code is PQM9EVM6.
NOTE: The current Host Code is PQM9EVM6. All online orders over $25 using this code will receive a sampler of designer series paper. You will also get a Happy Stamper Token for each $50 product increment on your order. See more about that popular program by clicking on Happy Stamper. If your order is over $150 in SU merchandise, please DO NOT use a hostess code. $150+ orders receive Stampin' Rewards and you don't want to miss out on getting your FREE stuff directly from Stampin' Up! And no worries, you will still get goodies from me such as Happy Stamper Tokens and a sampler of designer series paper.


It runs at 1200 times an hour. This machine can be set manually / semi automatic / fully automatic three modes, printing action indirect time can be digitally controlled.
Maintain。 The utility model has the advantages of safety, beautiful appearance, simple operation and convenient fetching, and greatly improves the production efficiency.
The microcomputer control with four key compilation action program, durable, easy to maintain.
All kinds of printing printing action design cycle, the user visible printing process of free choice.
The scraper constant pressure device, ensure the stability of the pressure in the printing process.
The scraper / ink reclaiming blade angle adjustable.
The high precision trimming table, with self-locking device, adjustment accuracy can reach 0.01MM.
The net frame position before and after about level adjustment.
The printing head upright lift function, convenient to take and put the screen.
The fine grinding of high-strength hardness worktable, ensure accurate multi-color printing.
The working table is equipped with emergency stop device, prevent hand pinch.
Trademark, IC board, film switch circuit, mobile phone lens, glass, liquid crystal display board and label and other flat material.


Offering supply chain management and a range of logistical services to clients from its headquarters in Phoenix, Arizona, GlobalTranz has enjoyed remarkable growth in recent years. In May 2017, GlobalTranz enjoyed recognition for its expansion when it earned the Association for Corporate Growth's (ACG) Arizona Deal of the Year Award.
The ACG provides a host of services to businesses in the middle market sector, including educational resources and advocacy. Beyond this, the ACG operates its JobSource platform to the benefit of job seekers and employers. The platform helps middle market professionals locate suitable roles while providing resources for employers so they can quickly sort through applications to located qualified candidates.
Employers also gain access to the ACG's Job Concierge service, through which the ACG helps them create job postings that are advertised on the JobSource platform for limited periods of time. Packages range from a single 30-day job posting, which provides full access to the candidate database for a $250.00 fee for members, up to a 10-job package costing $1,895.00 for members.


The long list of mind-boggling places to visit in Andaman that'll make your holiday absolutely unforgettable. A heven for honeymooners, adventurous spot for diving lovers and an idyllic island for a peaceful family getaway. These places will greet you with charming experiences on your Andaman Holiday.
As Solitary Confinement built by British in 1896. Visit Timing is 9.00 am to 12.30 pm & 1.30 pm to 4.45 pm.
It is the finest beach in Asia. It is an ideal place for swimming, sea bathing and basking on the sun kissed beach.
The island is presenting the ruins of old buildings all in dilapidated condition and is controlled by the Indian navy.
It is very famous for underwater corals and the pristine clear beach. This place is one hour journey from Wandoor beach.
It is an ideal place for you to enjoy a picnic lunch, or go snorkelling and enjoy watching colourful corals up to 20 metres depth.
It is popular for trekking and perfect for adventure seekers. Kalpong, the only river of Andamans flows through the forest.


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FarOut and GoRafting.com Collaborate to Offer Detailed Guides to the Best Whitewater Rafting and Kayaking in the United States and Beyond
Cathy Herbstler, Cherb PR
cathy@cherbpr.com / 206.390.0531
DENVER, CO (July 6, 2022) – FarOut, the leading creator of mobile app navigational guides for long-distance adventurers, and GoRafting.com, the originator of over 43 detailed whitewater guides, have teamed up to provide mobile access to the best whitewater rafting and kayaking guides in the U.S. and internationally. FarOut and GoRafting.com are a natural fit due to the detailed format of their guides.
"The GoRafting.com team is thrilled to partner with FarOut given their long-standing reputation for publishing comprehensive, quality guides," said Matt Volpert, CEO of GoRafting.com. "The FarOut app has data rich waypoints and navigation, including photos, multiple view options, and waypoint commenting, which is ideal for disseminating the detailed information we provide in the GoRafting.com guides."
"By partnering with GoRafting.com, FarOut can now expand beyond our trail guides to scenic rivers and beyond, providing our customers a more diverse outdoor adventure offering," said Paul Bodnar, CEO of FarOut. "The GoRafting.com network includes detailed whitewater guides in 14 states in the United States and internationally, including Costa Rica, Chile, and Iceland. We're excited for this opportunity to grow, and it has been a blast working with the team at GoRafting.com. We share the mission of creating the best guides out there."
FarOut released the first GoRafting.com guide, Grand Canyon Whitewater Guide, in February 2022. To date, FarOut has released the following seven GoRafting.com whitewater guides which are part of the Whitewater Classics Bundle – 550 miles of river adventure:
Río Futaleufú Whitewater Guide, Chile
Grand Canyon Whitewater Guide, Colorado River in Arizona
Kern River Whitewater Guide, California
Middle Fork of the Salmon River Whitewater Guide, Idaho
Upper Klamath Whitewater Guide, California & Oregon
Wild & Scenic Rogue River Whitewater Guide, Oregon
Nugget Section of the Rogue River Whitewater Guide, Oregon (free demo)
FarOut and GoRafting.com plan to release a dozen more whitewater rafting and kayaking guides in 2022, and will continue to curate and release guides moving forward.
About FarOut
FarOut, formerly known as Guthook Guides, is the leading creator of mobile app navigational guides for long-distance adventurers. Founders Paul Bodnar and Ryan Linn met while thru-hiking the Pacific Crest Trail in 2010 and teamed up to launch their first product, "Guthook's Guide to the Pacific Crest Trail" for iPhone in 2012. Today FarOut is the No. 1 app for long-distance hiking, biking, and paddling, with over 100 detailed guides around the world.FarOut is headquartered in Denver, Colorado, and is composed of a small team of experienced long-distance backpackers and hikers committed to partnering with trail organizations to create the highest quality navigational guides available. For more information, please visit https://faroutguides.com or email hello@faroutguides.com.
About GoRafting.com
Launched in 2020, GoRafting.com writes detailed whitewater guides for rafting and kayaking enthusiasts. By pairing extensive professional guiding and expedition experience with help from industry partners, the GoRafting.com team has published modern guidebooks for 43 rivers across the globe.


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Research ArticleAIDS/HIVImmunology Free access | 10.1172/JCI129161
SIV-specific CD8+ T cells are clonotypically distinct across lymphoid and mucosal tissues
Carly E. Starke,1 Carol L. Vinton,1 Kristin Ladell,2 James E. McLaren,2 Alexandra M. Ortiz,1 Joseph C. Mudd,1 Jacob K. Flynn,1 Stephen H. Lai,1 Fan Wu,3 Vanessa M. Hirsch,3 Samuel Darko,4 Daniel C. Douek,4 David A. Price,2,4,5 and Jason M. Brenchley1
1Barrier Immunity Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
2Division of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, United Kingdom.
3Nonhuman Primate Virology Section, Laboratory of Molecular Microbiology, and
4Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
5Systems Immunity Research Institute, Cardiff University School of Medicine, Heath Park, Cardiff, United Kingdom.
Address correspondence to: Jason M. Brenchley, 4 Memorial Drive, Room 211, 9000 Rockville Pike, Bethesda, Maryland 20892, USA. Phone: 301.496.1498; Email: jbrenchl@niaid.nih.gov.
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Received: March 28, 2019; Accepted: October 22, 2019
CD8+ T cell responses are necessary for immune control of simian immunodeficiency virus (SIV). However, the key parameters that dictate antiviral potency remain elusive, conceivably because most studies to date have been restricted to analyses of circulating CD8+ T cells. We conducted a detailed clonotypic, functional, and phenotypic survey of SIV-specific CD8+ T cells across multiple anatomical sites in chronically infected rhesus macaques with high (>10,000 copies/mL plasma) or low burdens of viral RNA (<10,000 copies/mL plasma). No significant differences in response magnitude were identified across anatomical compartments. Rhesus macaques with low viral loads (VLs) harbored higher frequencies of polyfunctional CXCR5+ SIV-specific CD8+ T cells in various lymphoid tissues and higher proportions of unique Gag-specific CD8+ T cell clonotypes in the mesenteric lymph nodes relative to rhesus macaques with high VLs. In addition, public Gag-specific CD8+ T cell clonotypes were more commonly shared across distinct anatomical sites than the corresponding private clonotypes, which tended to form tissue-specific repertoires, especially in the peripheral blood and the gastrointestinal tract. Collectively, these data suggest that functionality and tissue localization are important determinants of CD8+ T cell–mediated efficacy against SIV.
CD8+ T cells are required to control human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) but largely fail to protect infected humans and monkeys from eventual progression to AIDS (1). These lentiviruses replicate primarily in lymphoid tissues and preferentially infect CD4+ follicular helper T (TFH) cells (2). Elite control of HIV/SIV replication has been attributed to various qualitative properties of virus-specific CD8+ T cells (3–8), including the expression of CXCR5, which allows follicular access and direct proximity to infected CD4+ TFH cells (2, 9, 10). However, most studies to date have been limited to evaluations of peripheral blood samples, which may not fully recapitulate the whole-body response to HIV/SIV.
Antigen-specific CD8+ T cell populations generally incorporate several clonotypes, defined by the expression of distinct T cell receptors (TCRs) (11, 12). The composite properties of these constituent clonotypes in turn dictate the overall functionality of a given antigen-specific CD8+ T cell population (13). In the context of HIV/SIV, morphologically constrained repertoires directed against biologically variable epitopes have been associated with reproducible patterns of viral escape (14), whereas certain aspects of morphologically diverse repertoires directed against biologically constrained epitopes have been associated with protection, including the early mobilization of public clonotypes (15), which are commonly generated via convergent recombination and therefore occur in multiple individuals (16, 17), and the subsequent mobilization of cross-reactive private clonotypes (18). It nonetheless remains unclear how SIV-specific CD8+ T cells traffick in vivo to mediate these effects at sites of viral replication.
Recent work has identified discrete subsets of tissue-resident memory T cells, which occupy various epithelial, lymphoid, and mucosal sites (19–22) and differ from circulating memory T cells (23), constitutively expressing the C-type lectin CD69 and lacking the lymph node (LN) homing markers CCR7 and CD62L (24). In line with this concept of localized adaptive immunity, previous studies have revealed a degree of clonotypic disparity between circulating and mucosal SIV-specific CD8+ T cells, both in the context of acute infection (25) and in response to vaccination (26). Similarly, tissue-resident CD8+ T cells isolated from the LNs of elite controllers in another study exhibited skewed clonotypic profiles relative to specificity-matched CD8+ T cells isolated from venous blood samples, whereas the corresponding CD69– HIV-specific CD8+ T cells were clonotypically similar across the same anatomical compartments (27). These data suggest that distinct clonotypes may occupy distinct tissue niches, but to date, a comprehensive survey has not been performed across multiple anatomical sites.
In this study, we compared the clonotypic, functional, and phenotypic characteristics of SIV-specific CD8+ T cells across matched samples of peripheral blood and various lymphoid and mucosal tissues isolated from chronically infected rhesus macaques with high (>10,000 RNA copies/mL plasma) or low viral loads (VLs) (<10,000 RNA copies/mL plasma). We found that public clonotypes were commonly shared across anatomical sites, whereas private clonotypes were more often tissue specific. In addition, we identified correlates of immune control, including the presence of polyfunctional CXCR5+ SIV-specific CD8+ T cells in lymphoid tissues, such as the spleen and various LNs.
SIV-specific CD8+ T cells occur at similar frequencies in lymphoid and mucosal tissues. In preliminary experiments, we used fluorochrome-labeled pentameric complexes of Mamu-A*01-CTPYDINQM Gag181–189 (CM9) and/or Mamu-A*02-YTSGPGIRY Nef159–167 (Nef) and Mamu-A*02-GSENLKSLY Gag71–79 (Gag) to evaluate the distribution of SIV-specific CD8+ T cells across matched samples of peripheral blood and various tissue homogenates obtained from chronically infected rhesus macaques with high (>10,000 RNA copies/mL plasma; n = 16) or low VLs (<10,000 RNA copies/mL plasma; n = 6) (Table 1 and Supplemental Figure 1; supplemental material available online with this article; https://doi.org/10.1172/JCI129161DS1). No significant anatomical differences in response magnitude were detected between or within these outcome-defined groups (Figure 1A). Accordingly, the frequency of SIV-specific CD8+ T cells in the spleen correlated with the frequencies of SIV-specific CD8+ T cells in the GI tract (Figure 1B), the peripheral blood, and the axillary/inguinal lymph nodes (ALNs/ILNs) (Table 2). In contrast, the frequency of SIV-specific CD8+ T cells in the peripheral blood correlated only with the frequency of SIV-specific CD8+ T cells in the spleen, and the frequency of SIV-specific CD8+ T cells in the mesenteric lymph nodes (MLNs) correlated only with the frequency of SIV-specific CD8+ T cells in the GI tract (Table 2).
SIV-specific CD8+ T cells occur at similar frequencies in lymphoid and mucosal tissues. (A) Frequency of SIV-specific (CM9/Nef/Gag) CD8+ T cells across various anatomical sites. Horizontal bars indicate median values. GI, gastrointestinal. (B) Correlation between the frequency of SIV-specific CD8+ T cells in the GI tract and the frequency of SIV-specific CD8+ T cells in the spleen. (C–E) Frequency correlations for CD27+ (C), CD28+ (D), and CD69+ SIV-specific CD8+ T cells (E) in the GI tract versus the spleen. Data were acquired from Mamu-A*01+ and Mamu-A*02+ rhesus macaques (n = 22). Significance was determined using the Wilcoxon rank sum test (A) or Spearman's rank correlation with linear regression (B–E).
Characteristics of rhesus macaques used in this study
Frequency correlations for SIV-specific CD8+ T cells across various anatomical sites
In further analyses, we compared the phenotypes of lymphoid and mucosal SIV-specific CD8+ T cells, focusing on expression of the costimulatory molecules CD27 and CD28 and the tissue residency marker CD69. Strong correlations were detected between SIV-specific CD8+ T cells in the spleen and SIV-specific CD8+ T cells in the GI tract with respect to the expression frequencies of CD27 (Figure 1C) and CD28 (Figure 1D). No such association was observed for CD69 (Figure 1E). It was also noted that CD27, CD28, and CD69 were not differentially expressed on the surface of SIV-specific CD8+ T cells as a function of VL (data not shown).
Expression of CXCR5 on SIV-specific CD8+ T cells correlates inversely with VL. As expected, higher frequencies of CD4+ T cells in the GI tract and higher numbers of CD4+ T cells in the peripheral blood were detected in rhesus macaques with low VLs relative to rhesus macaques with high VLs (Figure 2, A and B). Moreover, the frequency of SIV-specific CD8+ T cells in the GI tract correlated with the frequency of CD4+ T cells in the GI tract and the number of CD4+ T cells in the peripheral blood (Figure 2, C and D).
Expression of CXCR5 on SIV-specific CD8+ T cells correlates inversely with VL. (A) Frequency of CD4+ T cells in the GI tract. (B) Number of CD4+ T cells in the peripheral blood. (C) Correlation between the frequency of SIV-specific CD8+ T cells in the GI tract and the frequency of CD4+ T cells in the GI tract. (D) Correlation between the frequency of SIV-specific CD8+ T cells in the GI tract and the number of CD4+ T cells in the peripheral blood. (E) Frequency of CXCR5+ SIV-specific CD8+ T cells in the spleen. (F) Correlation between the frequency of CXCR5+ SIV-specific CD8+ T cells in the spleen and the amount of viral DNA in CD4+ TFH cells. (G) Correlation between the frequency of CXCR5+ SIV-specific CD8+ T cells in the spleen and VL. Data were acquired from Mamu-A*01+ and Mamu-A*02+ rhesus macaques (n = 22). Horizontal bars indicate median values (A, B, and E). Significance was determined using the Mann-Whitney U test (A, B, and E) or Spearman's rank correlation with linear regression (C, D, F, and G).
Earlier work suggested that SIV-specific CD8+ T cells can enter lymphoid follicles in Asian macaques with low VLs (9, 10). In line with this observation, we found higher frequencies of CXCR5+ SIV-specific CD8+ T cells in the spleens of rhesus macaques with low VLs relative to rhesus macaques with high VLs (Figure 2E). To assess the biological relevance of this association, we measured SIV gag DNA in flow-sorted CD4+ TFH cells from the same tissues (Supplemental Figure 2). The frequency of CXCR5+ SIV-specific CD8+ T cells in the spleen correlated inversely with the amount of CD4+ TFH cell–associated viral DNA (Figure 2F) and the plasma burden of viral RNA (Figure 2G).
SIV-specific CD8+ T cells are polyfunctional in rhesus macaques with low VLs. To extend these findings, we assessed the functionality of SIV-specific CD8+ T cells in response to cognate peptide stimulation, measuring surface mobilization of CD107a and the simultaneous induction of IFN-γ, IL-2, IL-21, and TNF-α. The inclusion of IL-21 in the readout was designed to identify TFH-like activity (28). Overall, SIV-specific CD8+ T cells were more polyfunctional in the ALNs/ILNs of rhesus macaques with low VLs relative to rhesus macaques with high VLs, but very few of these cells in either group produced IL-21 (Figure 3A).
SIV-specific CD8+ T cells are polyfunctional in rhesus macaques with low VLs. (A) Pie charts depict relative expression of CD107a, IFN-γ, IL-2, IL-21, and/or TNF-α among memory CD8+ T cells in response to stimulation of ALNs/ILNs with overlapping peptides spanning SIV Gag (n = 6 Mamu-A*01+ rhesus macaques per group). (B) Pie charts depict relative expression of CD107a, granzyme B, IFN-γ, MIP-1β, RANTES, and/or TNF-α among CXCR5+ or CXCR5– memory CD8+ T cells in response to stimulation of splenocytes with overlapping peptides spanning SIV Gag (n = 4 Mamu-A*01+ rhesus macaques per group). Significance was determined using the permutation test in Simplified Presentation of Incredibly Complex Evaluations (SPICE) (detailed in Table 3).
In similar experiments, we compared the functionality of CXCR5+ and CXCR5– SIV-specific CD8+ T cells, measuring surface mobilization of CD107a and intracellular granzyme B, IFN-γ, macrophage inflammatory protein–1β (MIP-1β), RANTES, and TNF-α. CXCR5+ SIV-specific CD8+ T cells were more polyfunctional in the spleens of rhesus macaques with low VLs relative to rhesus macaques with high VLs and produced a wider range of effector molecules relative to CXCR5– SIV-specific CD8+ T cells (Figure 3B and Table 3).
Functionality comparisons for CXCR5+ versus CXCR5– memory CD8+ T cells in rhesus macaques with high versus low VLs
SIV-specific CD8+ T cell clonotypes targeting CM9 are structurally diverse. The early mobilization of public clonotypes and the subsequent mobilization of cross-reactive private clonotypes directed against biologically constrained epitopes have been associated with enhanced control of HIV/SIV (15, 18). We therefore used an unbiased molecular approach to characterize all expressed TCRβ locus (TRB) gene rearrangements in flow-sorted Mamu-A*01–restricted CM9-specific CD8+ T cell populations (Supplemental Figure 2) isolated at necropsy from each anatomical site in rhesus macaques with high (Supplemental Figure 3) or low VLs (Supplemental Figure 4). Data were normalized before analysis to correct for differences in sample size (29, 30). The number of unique clonotypes per anatomical site was similar in rhesus macaques with high (median 6, range 1–16) and low VLs (median 7, range 1–13). Moreover, no consistent anatomical differences in repertoire diversity were apparent between or within these outcome-defined groups, and accordingly, no correlations were detected between repertoire diversity and either the amount of CD4+ TFH cell–associated viral DNA or the plasma burden of viral RNA (data not shown and Figure 4A). There were some conspicuous anatomical differences in repertoire similarity, however, most notably between lymphoid and mucosal sites in certain rhesus macaques with high or low VLs (Figure 4B).
Clonotypic architecture of CM9-specific CD8+ T cell populations. (A) Repertoire diversity in rhesus macaques with high (n = 6) or low VLs (n = 6). (B) Repertoire similarity in rhesus macaques with high (n = 6) or low VLs (n = 6). (C) TRBV gene use in rhesus macaques with high VLs (n = 6). (D) TRBV gene use in rhesus macaques with low VLs (n = 6). (E) CDR3β amino acid use in rhesus macaques with high VLs (n = 6). (F) CDR3β amino acid use in rhesus macaques with low VLs (n = 6). Significance was determined using the permutation test in SPICE (C and D).
A vast majority of CM9-specific clonotypes in both groups incorporated CDR3β loops spanning 14 amino acids, with equivalent representation at each anatomical site (Supplemental Figure 5). Irrespective of anatomical location, preferential use of TRBV6-1 and TRBV9 was observed in rhesus macaques with high VLs (Figure 4C), and preferential use of TRBV6-1, TRBV10-2, and TRBV13 was observed in rhesus macaques with low VLs (Figure 4D). Similarly, preferential use of TRBJ1-5 and TRBJ2-1 was observed in rhesus macaques with high VLs (Supplemental Figure 6A), and preferential use of TRBJ1-5 was observed in rhesus macaques with low VLs (Supplemental Figure 6B). No clear motifs were observed among non–germline-encoded CDR3β residues, irrespective of VL (Figure 4, E and F).
SIV-specific CD8+ T cell clonotypes targeting CM9 are anatomically discrete. To substantiate the observed anatomical differences in repertoire similarity, we assessed the distribution of CM9-specific clonotypes across peripheral blood and tissue sites, again comparing rhesus macaques with high versus low VLs. A degree of clonotype sharing was apparent in each individual rhesus macaque, most notably between the spleen and the peripheral blood and between the MLNs and the GI tract (Figure 5, A and B). However, many clonotypes were either unique to a particular anatomical site or preferentially located in a particular anatomical site, most commonly the GI tract (Figure 5, A and B). No obvious anatomical differences in clonotype sharing were detected between groups, although unique clonotypes were significantly more common in the MLNs of rhesus macaques with low VLs relative to rhesus macaques with high VLs (Figure 5C). Equivalent levels of sharing between groups were also observed for clonotypes stratified by the number of occupied sites (Figure 5D). In general, the number of anatomical sites occupied by a given clonotype increased as the frequency of a given clonotype increased at any given anatomical site, and this was true across all sampled tissues (Figure 5E and Table 4). However, there were exceptions to this pattern, especially in the GI tract, where some clonotypes occurred at high frequencies with no sharing (e.g., rhesus macaque 591) or sharing restricted to the MLNs (e.g., rhesus macaque 863), and other clonotypes occurred at low frequencies with sharing across all anatomical sites (e.g., rhesus macaques 760 and F98) (Figure 5, A and B). Moreover, approximately 40% of clonotypes were unique to each site, rising to more than 55% in the peripheral blood and the GI tract, and most of the shared clonotypes in the peripheral blood were found in the spleen but not in the GI tract (Figure 5F). These clonotypically distinct SIV-specific CD8+ T cell populations were nonetheless functionally equivalent across various tissue sites, at least after stimulation with nonlimiting concentrations of CM9 (Figure 5G).
CM9-specific CD8+ T cell clonotypes are anatomically discrete. (A) Frequency of individual clonotypes across various anatomical sites in rhesus macaques with high VLs. (B) Frequency of individual clonotypes across various anatomical sites in rhesus macaques with low VLs. (C) Proportion of clonotypes detected in 1 (unique) or more than 1 (shared) anatomical site in rhesus macaques with high (n = 6) or low VLs (n = 6). Significance was determined using the χ2 test. **P < 0.01. (D) Proportion of clonotypes shared across the indicated number of anatomical sites in rhesus macaques with high (n = 6) or low VLs (n = 6). Significance was determined using the Mann-Whitney U test. (E) Correlation between the number of occupied anatomical sites and clonotype frequency in the GI tract. Significance was determined using Spearman's rank correlation with linear regression. (F) Schematic representation of clonotype sharing across distinct anatomical sites (n = 12 Mamu-A*01+ rhesus macaques). Values in parentheses refer to unique clonotypes at each anatomical site (%). (G) Pie charts depict relative expression of CD107a, IFN-γ, MIP-1β, RANTES, and/or TNF-α among clonotypically distinct (TCR Vβ1+ or TCR Vβ23+) CM9-specific memory CD8+ T cells in response to stimulation of various tissue homogenates with overlapping peptides spanning SIV Gag (n = 4 Mamu-A*01+ rhesus macaques per group). Clonotypes found in multiple tissues (circulating) were distinguished from clonotypes found in 1 tissue (resident). Significance was determined using the permutation test in SPICE.
Correlations between the number of occupied anatomical sites and clonotype frequency at each anatomical site
Public clonotypes were identified on the basis of sharing at the amino acid level across more than 1 rhesus macaque in our cohort and/or across previously reported data sets from other rhesus macaques (refs. 14, 15, 31 and Figure 6, A and B). No significant differences in the anatomical distribution of public clonotypes were detected between or within groups (Figure 6C). However, public clonotypes with identical nucleotide sequences were shared across anatomical sites more commonly than private clonotypes in individual rhesus macaques, irrespective of VL (Figure 6D).
Public CM9-specific CD8+ T cell clonotypes are commonly shared across multiple anatomical sites. (A) Frequency of public (colored bars) or private clonotypes (white bars) across various anatomical sites in rhesus macaques with high VLs. (B) Frequency of public (colored bars) or private clonotypes (white bars) across various anatomical sites in rhesus macaques with low VLs. (C) Proportion of public or private clonotypes detected at each anatomical site in rhesus macaques with high (n = 6) or low VLs (n = 6). Significance was determined using the χ2 test. (D) Proportion of public or private clonotypes shared across the indicated number of anatomical sites in Mamu-A*01+ rhesus macaques (n = 12). Significance was determined using the Mann-Whitney U test.
Virus-specific CD8+ T cells are necessary for the control of HIV and SIV (32–34). However, the precise determinants of immune efficacy remain unclear, potentially because current paradigms are based primarily on studies of circulating CD8+ T cells. We report here that SIV-specific CD8+ T cells are clonotypically distinct across multiple anatomical compartments in rhesus macaques with chronic infection or AIDS. Public clonotypes were commonly shared across anatomical sites in individual rhesus macaques, as were the more dominant clonotypes at any particular anatomical site, but overall, approximately 40% of clonotypes were site specific, and unique clonotypes were observed most often in the peripheral blood and the GI tract. Moreover, rhesus macaques with low VLs harbored higher frequencies of polyfunctional CXCR5+ SIV-specific CD8+ T cells in various lymphoid tissues, such as the spleen and the ALNs/ILNs.
Expression of CXCR5 is required for entry into B cell follicles (35, 36). We found that the frequency of CXCR5+ SIV-specific CD8+ T cells in the spleen correlated inversely with viral replication, measured in terms of CD4+ TFH cell–associated viral DNA and plasma viral RNA. Although these findings are consistent with the hypothesis that follicular access licenses the optimal delivery of antiviral effector functions (37–39), it is important to note that high levels of antigen expression can exhaust follicular CXCR5+ virus-specific CD8+ T cells as a consequence of sustained activation via the TCR (40). This phenomenon may explain, at least in part, the preferential occurrence of CXCR5+ SIV-specific CD8+ T cells in rhesus macaques with low VLs. Follicular CXCR5+ SIV-specific CD8+ T cells are nonetheless optimally positioned to suppress viral replication in vivo, potentially via noncytolytic mechanisms (41).
Our current understanding of HIV/SIV-specific CD8+ T cell responses is derived mainly from studies of peripheral blood, which is easily accessible in humans and other primates (1, 3, 4, 14, 15, 18, 32–34, 42). Other windows may provide better insights, however, because these viruses replicate in lymphoid tissues, and very few lymphocytes in the total body pool circulate at any given time (43). In line with previous studies, we found a degree of clonotype sharing across anatomical compartments (25, 26, 44), which has likewise been reported in the context of influenza virus infection (45). However, we also identified anatomically unique clonotypes, most frequently in the peripheral blood and the GI tract. The clonotypic disparity between peripheral blood and lymphoid tissues is consistent with the recent description of tissue-resident HIV-specific CD8+ T cells (27), which provide durable antiviral immunity at the site(s) of viral challenge/replication (27, 46, 47). Our data therefore suggest 2 mutually inclusive possibilities. The first is that individual CD8+ T cells are primed in situ and do not traffick extensively between anatomical compartments during chronic infection, implying that systemic vaccination may be required to elicit long-term immunity against HIV/SIV (26). The second is that public clonotypes are more readily primed during the early stages of infection as a function of prevalence within the naive pool, which can be attributed to convergent recombination (48, 49), and subsequently form highly stable tissue-resident populations, which are then more likely to be shared across sites of viral replication (27, 50). Longitudinal studies will be necessary to address these possibilities and determine which route(s) of vaccine delivery are likely to favor the generation of effective immunity against HIV/SIV.
In summary, we have demonstrated that SIV-specific CD8+ T cells are clonotypically, functionally, and phenotypically distinct across multiple anatomical sites in outcome-defined groups of rhesus macaques with chronic infection or AIDS. A greater understanding of these anatomical complexities may therefore be required to identify the key attributes of effective virus-specific CD8+ T cell responses, which in turn may inform the rational design of next-generation vaccines against HIV/SIV.
Study design. The goal of this study was to assess the functional and phenotypic characteristics of SIV-specific CD8+ T cell clonotypes across distinct anatomical compartments in rhesus macaques (Macaca mulatta) with high (>10,000 RNA copies/mL plasma; n = 16) or low VLs (<10,000 RNA copies/mL plasma; n = 6) during the chronic phase of infection with SIVmac239, SIVsmE543, or SIVsmE660 (Table 1 and Supplemental Figure 1). Selection criteria included the availability of cryopreserved tissue homogenates. PBMCs, spleen, ALNs, ILNs, MLNs, colon, and jejunum were obtained at necropsy from Mamu-A*01+ (n = 12) and Mamu-A*02+ rhesus macaques (n = 11) with established SIV infection or AIDS (Table 1). Samples were homogenized as described previously (51). Clinical endpoints were defined as (a) weight loss more than 25%; (b) major organ failure or medical conditions unresponsive to treatment; (c) complete anorexia for 4 days; (d) inability to consume sufficient nutrients to maintain body weight without assistance for 7 days; (e) distress vocalization unresponsive to intervention for 7 days; and/or (f) tumors arising from other than experimental means that impaired movement, ulcerated, or grew to more than 10% of body weight. Euthanasia was performed according to guidelines established by the American Veterinary Medical Association.
Flow cytometric sorting of SIV-specific CD8+ T cells. Tissue homogenates were washed twice in RPMI 1640 medium supplemented with 10% fetal bovine serum, 2 mM l-glutamine, and 1% penicillin/streptomycin (all from HyClone, GE Healthcare Life Sciences). SIV-specific CD8+ T cells were identified using CM9 and/or Nef and Gag Pro5 MHC Class I Pentamers (ProImmune). Surface markers were identified using pretitrated concentrations of the following antibodies: (a) anti-CD8a (RPA-T8) and anti-CXCR5 (MU5UBEE) from eBioscience; (b) anti-CD3 (SP34-2), anti-CD8a (SK1), anti-CD27 (O323), anti-CD69 (FN50), and anti-CCR7 (3D12) from BD Biosciences; (c) anti-CD4 (OKT4), anti-CD95 (DX2), and anti–PD-1 (EH12.2H7) from BioLegend; and (d) anti-CD28 (CD28.2) from Beckman Coulter. Bulk CD4+ TFH cells and SIV-specific CD8+ T cells were flow-sorted using a FACSAria (BD Biosciences). Bulk CD4+ TFH cells were defined as live, CD3+, CD4+, CD28+, CD95+, CXCR5+, PD-1+ lymphocytes, and SIV-specific CD8+ T cells were defined as live, CD3+, CD8+, CM9/Nef/Gag+ lymphocytes (Supplemental Figure 2).
Functional analysis of SIV-specific CD8+ T cells. Cell suspensions were stimulated with a pool of peptides spanning SIV Gag (15-mers overlapping by 11 amino acids) at a final concentration of 2 μg/peptide/106 cells in the presence of anti-CD28 (CD28.2; Beckman Coulter), anti-CD107a (H4A3; BioLegend), brefeldin A (1 μg/mL; MilliporeSigma), and monensin (1 μg/mL; BD Biosciences) for 16 hours at 37°C. After stimulation, cells were washed in PBS, stained for surface markers, fixed/permeabilized, and stained for intracellular markers. The following antibodies were used in these experiments: (a) anti-CD4 (OKT4), anti-CXCR5 (MU5UBEE), and anti–IL-21 (3A3-N2) from eBioscience; (b) anti-CD3 (SP34-2), anti-CD8a (SK1), anti-CD95 (DX2), anti–granzyme B (GB11), anti–IL-2 (MQ1-17H12), anti–MIP-1β (D21-1351), and anti-RANTES (2D5) from BD Biosciences; (c) anti–IFN-γ (4S.B3) and anti–TNF-α (MAb11) from BioLegend; and (d) anti–TCR Vβ1 (BL37.2) and anti–TCR Vβ23 (AF23) from Beckman Coulter. Data were acquired using an LSR Fortessa (BD Biosciences). SIV-specific CD8+ T cells were defined as live, CD3+, CD8+, function+/pentamer+ lymphocytes (Supplemental Figure 2). Functional profiles were analyzed using SPICE v5.35 (National Institute of Allergy and Infectious Diseases).
Quantification of cell-associated SIV DNA. SIV DNA was quantified in CD4+ TFH cells as described previously (52, 53). Briefly, flow-sorted cells were lyzed using 25 μL of a 1:100 dilution of proteinase K (Roche) in 10 mM Tris-HCl (pH 8.4). Quantitative PCRs were performed in duplicate using 5 μL of cell lysate per reaction with TaqMan Master Mix (Thermo Fisher Scientific) over 50 cycles of 95°C for 15 seconds and 60°C for 1 minute after a single holding step of 95°C for 5 minutes. SIVmac239 gag was amplified using the forward primer GTCTGCGTCATYTGGTGCATTC and the reverse primer CACTAGYTGTCTCTGCACTATRTGTTTTG with the probe CTTCRTCAGTYTGTTTCACTTTCTCTTCTGCG. SIVsmE543/smE660 gag was amplified using the forward primer GGCAGGAAAATCCCTAGCAG and the reverse primer GCCCTTACTGCCTTCACTCA with the probe AGTCCCTGTTCRGGCGCCAA. Cell numbers were quantified relative to monkey albumin (54). Reactions were processed using a StepOnePlus Real-Time PCR System (Applied Biosystems, Thermo Fisher Scientific), and template copies were calculated using StepOne Software (Applied Biosystems, Thermo Fisher Scientific).
Clonotype analysis. Pentamer-labeled CD8+ T cells were flow-sorted viably into 100 μL of RNAlater (MilliporeSigma). All expressed TRB gene rearrangements were amplified without bias using a template-switch anchored reverse transcription PCR as described previously (55). Sequences were aligned using Sequencher v5.4.6 (Gene Codes Corporation). TRBV and TRBJ genes were identified according to the ImMunoGeneTics nomenclature (56). Data were normalized using a randomization procedure to account for differences in sample size as described previously (29, 30). Repertoire diversity was assessed using the Shannon diversity index (29), and repertoire similarity was assessed using the Morisita-Horn similarity index (30). Anatomical overlap was visualized using Circos (http://circos.ca/) and InteractiVenn (http://www.interactivenn.net/), and amino acid use was visualized using WebLogo (https://weblogo.berkeley.edu/).
Statistics. Matched groups were compared using the Wilcoxon rank sum test. Unmatched groups were compared using the Mann-Whitney U test. Correlations were evaluated using Spearman's rank correlation with linear regression. Proportions were compared using the χ2 test. All statistical analyses were performed using Prism v7.0 (GraphPad Software Inc.). P values less than 0.05 were considered significant. Functional profiles were compared using the permutation test with relative expression values in SPICE v5.35 (National Institute of Allergy and Infectious Diseases).
Study approval. Experimental procedures were approved by the National Institute of Allergy and Infectious Diseases Division of Intramural Research Animal Care and Use Program as part of the NIH Intramural Research Program (protocols LMM6 and LVD26). Rhesus macaques were housed and sustained in accordance with standards established by the Association for Assessment and Accreditation of Laboratory Animal Care.
CES, CLV, AMO, JCM, JKF, SHL, FW, and JMB performed experiments. CES, CLV, JCM, SD, and JMB analyzed data. KL, JEM, AMO, FW, VMH, DCD, and DAP provided critical resources. CES and JMB designed the project. CES, DAP, and JMB wrote the manuscript.
We thank Heather Kendall, JoAnne Swerczek, Richard Herbert, and all veterinary staff at the NIH Animal Center. This study was supported in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH. DAP is a Wellcome Trust Senior Investigator (100326/Z/12/Z).
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Version 2 (January 6, 2020): Electronic publication


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Home News National ID System to Unify Government-Issued ID cards, Ease Delivery of Social...
National ID System to Unify Government-Issued ID cards, Ease Delivery of Social Services
By Mini
MANILA, Philippines- A national ID system that will replace all-government-issued identification cards, except the driver's license and passport, will be issued to all 105 million Filipinos within President Rodrigo Duterte's term.
Aside from unifying all government IDs, the national ID will also function as a social welfare card to ease the delivery of social services, according to a report by ABS-CBN News.
PHOTO CREDIT: ABS-CBN News
"The national ID will also function [as a] social welfare card. This will identify the qualified beneficiaries, and discounts of transportation, and health care. This will help us plug the leaks in the social welfare program," Budget Secretary Benjamin Diokno said on Wednesday, July 5.
The national ID, which will contain the individual's personal information and biometric data, will be issued at birth and renewable when the citizen turns 18. It will also contain information to determine if an individual can avail of subsidies; discounts on medicine, health care services and transportation; and tax exemptions under the law and the Tax Reform for Acceleration and Inclusion (TRAIN) Act.
Secured with Europay, Mastercard, Visa (EMV) chips, the ID will possibly load cash subsidies for individuals legally entitled to such benefits.
Once the House enacts a law establishing a national ID system, IDs will be issued initially to senior citizens and persons with disabilities. Members of the 5.2 million poorest household in the country not yet covered by the Department of Social Welfare and Development's (DSWD) conditional cash transfer program will also be prioritized.
Finance Undersecretary Karl Kendrick Chua said the IDs will be issued within two years of the enactment of the national ID system law.
"The Philippine Statistics Authority (PSA) will issue the ID cards, with the National Economic and Development Authority (NEDA) providing oversight functions. The DSWD, meanwhile, will coordinate the various social benefit programs that will be put in place under TRAIN," Chua said.
social welfare card
McDonalds To Follow Suit And Raise Their Beverage Prices
Grab Facing P6.5M Fine for Submitting Insufficient Price Monitoring Data
GDP Growth Rate under Duterte Admin's First Year Highest Among Previous...
Italy Extends Development Loan Assistance to the Philippines


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Professional Zodiac Bulk Packs of Spot On Topical Flea & Tick Treatment for Dogs(4 Vials) - Dogs 7 to 17 lbs -1 applicator 1/2 at the base of neck, 1/2 at base of tail. Professional zodiac bulk packs of spot on topical flea & tick treatment for dogs protect your poochies against biting insect with our zodiac spot on flea & tick treatment bulk packs. Exported by exportyourstore. Keep cats away from treated dogs until application site is dry to the touch. 00%not for use on cats. Dosage the number of vials to be applied depends on the weight of the dog. Dogs greater than 55 lbs, 5 applicators distribute in 5 spots down the middle of the back. Kills and repels adult fleas, ticks, and mosquitoes for up to 30 dayscontains precor igr to prevent eggs from hatchingeconomical bulk pack contains 48 applicationssafe for dogs 6 months and older each applicator tube contains 0. Convenient zodiac spot on flea and tick treatment groomer's pack gives you an easy way to add flea and tick treatment to your services. 65 cc of spot on treatment for dogs only. Active ingredientspercentagepermethrin (cas #52645-53-1)45%(s)-methoprene (cas #65733-16-6)3%other ingredients52%total100. May be toxic and potentially fatal if applied to or ingested by cats. If this occurs, immediate veterinary care should be provided. Dogs 18 to 35 lbs, 2 applicators, 1 at base of neck, 1 at base of tail. Accidental application to cats and/or grooming a recently treated dog may result in tremors and/or uncoordinated muscle movements. Cats that actively groom or engage in close physical contact with recently treated dogs may be at risk of serious harmful effects. Dogs 36 to 55 lbs, 3 applicators, 1 at base of neck, 1 in middle of back, 1 at tail.
PetAction Plus Flea & Tick Treatment for Cats Over 1.5 lbs, 3 Month Supply - Contains the same active ingredients found in frontline plus for cats. Medication remains effective even after bathing, water immersion, or exposure to sunlight. Kills fleas, flea eggs and larvae, chewing lice and ticks. Fast-acting, long-lasting, and waterproof flea and tick treatment for your pets. Aids in the control of sarcoptic mange mite infestation.
Professional Zodiac Bulk Packs of Spot On Topical Flea & Tick Treatment for Dogs(8 Vials) - Accidental application to cats and/or grooming a recently treated dog may result in tremors and/or uncoordinated muscle movements. Dogs 36 to 55 lbs, 3 applicators, 1 at base of neck, 1 in middle of back, 1 at tail. Exported by exportyourstore. Convenient zodiac spot on flea and tick treatment groomer's pack gives you an easy way to add flea and tick treatment to your services. Dogs 7 to 17 lbs -1 applicator 1/2 at the base of neck, 1/2 at base of tail. Active ingredientspercentagepermethrin (cas #52645-53-1)45%(s)-methoprene (cas #65733-16-6)3%other ingredients52%total100. Kills and repels adult fleas, ticks, and mosquitoes for up to 30 dayscontains precor igr to prevent eggs from hatchingeconomical bulk pack contains 48 applicationssafe for dogs 6 months and older each applicator tube contains 0. May be toxic and potentially fatal if applied to or ingested by cats. Professional zodiac bulk packs of spot on topical flea & tick treatment for dogs protect your poochies against biting insect with our zodiac spot on flea & tick treatment bulk packs. Dogs greater than 55 lbs, 5 applicators distribute in 5 spots down the middle of the back. Keep cats away from treated dogs until application site is dry to the touch. 65 cc of spot on treatment for dogs only. Dogs 18 to 35 lbs, 2 applicators, 1 at base of neck, 1 at base of tail. 00%not for use on cats. Dosage the number of vials to be applied depends on the weight of the dog. If this occurs, immediate veterinary care should be provided. Cats that actively groom or engage in close physical contact with recently treated dogs may be at risk of serious harmful effects.
Professional Zodiac Bulk Packs of Spot On Topical Flea & Tick Treatment for Dogs(16 Vials) - 00%not for use on cats. Convenient zodiac spot on flea and tick treatment groomer's pack gives you an easy way to add flea and tick treatment to your services. Dogs 36 to 55 lbs, 3 applicators, 1 at base of neck, 1 in middle of back, 1 at tail. Exported by exportyourstore. Keep cats away from treated dogs until application site is dry to the touch. Active ingredientspercentagepermethrin (cas #52645-53-1)45%(s)-methoprene (cas #65733-16-6)3%other ingredients52%total100. Dogs greater than 55 lbs, 5 applicators distribute in 5 spots down the middle of the back. Professional zodiac bulk packs of spot on topical flea & tick treatment for dogs protect your poochies against biting insect with our zodiac spot on flea & tick treatment bulk packs. Cats that actively groom or engage in close physical contact with recently treated dogs may be at risk of serious harmful effects. If this occurs, immediate veterinary care should be provided. May be toxic and potentially fatal if applied to or ingested by cats. 65 cc of spot on treatment for dogs only. Dosage the number of vials to be applied depends on the weight of the dog. Dogs 7 to 17 lbs -1 applicator 1/2 at the base of neck, 1/2 at base of tail. Dogs 18 to 35 lbs, 2 applicators, 1 at base of neck, 1 at base of tail. Accidental application to cats and/or grooming a recently treated dog may result in tremors and/or uncoordinated muscle movements. Kills and repels adult fleas, ticks, and mosquitoes for up to 30 dayscontains precor igr to prevent eggs from hatchingeconomical bulk pack contains 48 applicationssafe for dogs 6 months and older each applicator tube contains 0.
Dog MD Plus 89-132 Lb Dog Flea & Tick Treatment 3 Count - . Dog md maximum defense plus has the same active ingredients as frontline plus. The fast-acting, long-lasting squeeze-on is formulated to protect your dog against dangerous pests including fleas, flea eggs, flea larvae, ticks and chewing lice. Dog md maximum defense plus, comparable to frontline plus provides the full-body protection your dog needs to stay flea and tick free. It breaks the flea life cycle by killing flea eggs and larvae and kills ticks that may transmit lyme disease.
UltraGuard One Spot Flea & Tick Treatment For Cats And Kittens - Kills and prevents flea eggs. Package contains 3 monthly treatments. Kills and prevents larvae. Do not use on kittens less than 12 weeks old.
UltraGuard Flea And Tick Treatment Drops For Dogs And Puppies - A powerful, effective insecticide that kills adult fleas, ticks and mosquitoes in the dog's environment specially formulated for dogs provides relief from flea infestations for one month by killing and preventing adult fleas by breaking the flea and tick life cycle kills the rocky mountain wood tick and deer tick which may carry lyme disease also kills and repels mosquitoes which may carry canine heartworms for dogs and puppies weighing 16 to 30 lbs 3 per card.
UltraGuard Plus Flea And Tick Treatment Powder - Total of 6 units. 4 oz unit size of measure. High quality. Buy in bulk and save. Brought to you by hartz.
3-doses 5-22 lbs Dogs Flea and Tick Treatment, Small, Orange - Kills all stages of 4 major ticks, including those that may carry lyme disease. Frontline plus provides a convenient spot treatment for fast-acting long lasting control of fleas, ticks and chewing lice. Contains 3 67 ml applicators providing 3 months of protection. Remains waterproof for 30 days even if your dog or cat swims or is bathed. Available in small size and orange color.
Frontline Flea and Tick Treatment Dog/Cat Spray, 8-1/2-Ounce - Contains fiprinol to kill pests quickly and safely safe for dogs, puppies, cats and kittens 8 weeks or older. Flea and tick treatment spray-on topical flea control formula can be applied directly to pets to provide fast-acting control of fleas and ticks for up to 30 days. Spray bottle is easy to use, ensures fast and even application and can be reapplied regularly. Epa reg no 65331-1. Kills fleas before they lay eggs, effectively preventing reinfestation.
Sentry FIPROGUARD PLUS for Dogs & Puppies 4-22 lbs. Topical Flea & Tick Treatment, 6 Month Supply - Contains fipronil and (s)-methoprene. Fast acting, long lasting, waterproof protection. Only for use on dogs & puppies over 8 weeks of age. Kills fleas, flea eggs, flea larvae, ticks and chewing lice.