text: Description Edit In Romanian: Glazura de ou Ingredients Edit 8 oz/250 g sugar 2 egg whites juice from 1 lemon (or orange) Directions Edit Mix the confectioner's sugar with the egg whites and the juice from 1 lemon or 1 orange. Stir for almost 1 hour until thick. Cover the cake with this paste. Retrieved from "https://recipes.fandom.com/wiki/Egg_Icing?oldid=643567" Categories: Romanian Desserts Frosting and icing Recipes Egg white Recipes Lemon juice Recipes Orange juice Recipes Recipes that need photos Community content is available under CC-BY-SA unless otherwise noted.


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re: could u plz help me
Although you can do it in visual c++ but I don't recommend using it for database programming. Use visual basic instead.
To download the source code please click the following links:
Hotel Reservation System (VB 6.0 Version)
Although you can do it in visual c++ but I don't recommend using it for database programming. Use visual basic instead.
Edit the business info in data.mdb database. To change the logo you need crystal reports 8.5.
The source code is available only for 2008 version and I don't have plan of making a 2005 version.
Sorry but I don't have payroll made in PHP.
Download my hotel reservation system and study it as long as you can so you will know how it works.
can u plz send me the source code of hotel management system in netbeans(6.5.1) connected to database mysql.
my id is [email protected]
Give us some portion of your work which you need help.
Your technique is redundant. If you see my hotel reservation system you do not need to call a procedure in order to know if the room is available. In my room window you'll already know if the room is vacant or not. I think this is the best solution for your problem. Just copy some code on my program and integrate it on your own.
Did you register the b8controls.ocx?
Read the readme.html inside a zip file and also the FAQ.
What is the subject of your email? So I can identify yours.
Use the contact page if you want to email me.

subset: commoncrawl


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ISBN Druckformat:
A DESULFURIZATION MATHEMATICAL MODEL AND A PILOT EXPERIMENT BY SPRAYING NaOH SOLUTION INTO DOWNSTREAM FLUE DUCT OF A COAL-FIRED INDUSTRIAL BOILER
HeSheng Zhang
In a wet desulfurization process NaOH solution is sprayed into flue duct, small droplets are then formed and react directly with gaseous SO2 in FG. In this paper a two-phase mathematical model based on dual film mass transfer theory and boundary layer theory on the surface of droplet is proposed to describe the reacting processes between the gaseous SO2 and a single droplet Then according to the droplet diameter distribution function, a set of formulas to estimate the binding capability of droplets on SO2 and to predict the desulfurization efficiency are established. Through numerical calculation, key factors such as pH value of droplets, the ratio of spraying NaOH solution volume to the volume of FG, etc. are analyzed and discussed. Additionally, a SO2 removal pilot experiment is carried out on the flue duct of a coal-fired industrial boiler with steam capacity of 10T/h to test the SO2 removal rate.


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After five days at sea, 230 migrants rescued off the coast of Libya by a German NGO will finally be landed on the Mediterranean island of Malta.
This was announced on Tuesday by Italian Prime Minister Giuseppe Conte, who assured that his Maltese counterpart, Joseph Muscat, confirmed by telephone this decision if other countries of the European Union (EU) agreed to receive some of these people.
In addition to Malta and Italy, France and Portugal have already announced that they will host part of the group of migrants in their territories.
According to Conte, Muscat told him that "the boat will be investigated to find out its effective nationality [bears the flag of the Netherlands] and if the rules of international law have been respected."
Following the recent experience of Aquarius boat, which was finally received by Spain with more than 600 people on board, the Italian Interior Minister, Matteo Salvini -Qu ien called "human flesh" to migrants- celebrated the future outcome of this case.
"And two! After the NGO Aquarius went to Spain, now it's up to the NGO Lifeline that will go to Malta, with this outlawed ship that will finally be kidnapped … For women and children fleeing the war the doors they are open, for the rest no!# stopinvasion, "Salvini posted on Facebook.
How a ship unleashed a crisis that threatens Europe's most powerful government
Spain accepts to receive the Aquarius, the ship with 629 immigrants adrift that Italy and Malta refused to accept
Therefore, some of the most common questions since this crisis in the Mediterranean erupted are: who is responsible for hosting migrant ships?And can a country, in effect, legally refuse to receive them?
The lack of a European solution
Generally speaking, a country can close its ports in the exercise of its sovereignty ed and prevent a ship from entering its territorial waters (up to 12 miles from the coastline).
A vessel requires permission to enter the territorial sea of a country. Once inside, however, it can no longer be rejected by the authorities for the assistance needs that passengers may have.
But, in parallel with this right of rejection, the country must also comply with the international obligation to receive those who are in danger at sea.
In other words, many suggest that countries must find a balance between "responsibility" and "solidarity" to comply with all laws. And reaching an agreement on this balance will also be one of the keys to the European summit on migration to be held this Thursday in Brussels.
When the BBC asked the European Commission for details on the legal responsibilities of its members on the ships that transport migrants, the institution referred to this means to the conventions and international maritime laws in force.
Among them, is the International Convention for the Safety of Human Life in the Sea of 1974, which indicates that any ship that has knowledge of people in danger "must proceed with their assistance as quickly as possible".
In addition, the United Nations Convention on the Law of the Sea of 1982 says that every State that has a ship with its flag raised should require that the ship rescue those "in danger" at sea.
For its part, according to the International Maritime Organization, which helped define some of the principles governing the rescue tasks at sea, its members also have the obligation to "coordinate so that people rescued at sea land in a safe place as soon as possible".
A question of definitions
The rules set on paper, however, have several interpretations when applied in practice.
One problem is usually how you define what is a situation of danger, according to Yves Pascouau, editor of the website of the European Migration Act which provides advice on asylum and immigration rules across the EU.
"This is a matter of interpretation," he says.
The Aquarius, for example, was not in obvious mechanical difficulties as it approached Maltese and Italian waters, so these countries " did not consider the definition of danger to be fulfilled ".
In addition, the Maltese authorities had provided some food and water to the people on board.
However, the ship was carrying more than one hundred unaccompanied minors and several pregnant women, many of them sleeping in the open.
The NGOs that operated the vessel argued that not allowing them to dock in Italy and having people on board spend more days at sea to get to Spain exposed them to greater difficulties.
Legal gaps
There are also different interpretations of what is considered to take migrants to "a safe place", and if that means exclusively landing on land.
"There is no obligation to receive survivors on land for a State responsible for a specific area of search and rescue or to coordinate rescue tasks," says Ainhoa Campas Velasco of the Maritime Law Institute of the University of Southampton, in the United Kingdom…
In the case of Aquarius, for example, it was Italy who was leading such work, since the Maritime Rescue Coordination Center of the Coast Guard of Rome is in charge of coordinating these actions when it receives an emergency warning in international waters of the Mediterranean more beyond the search and rescue zones of each country.
However, Campas Velasco points out that humanitarian considerations should also be part of search and rescue operations.
Human rights organizations say that migrants face serious dangers in Libya at the hands of militias and groups that smuggle people. They also argue that people fleeing war and persecution have the right to asylum.
However, it is important to remember that the reception of migrants seeking asylum in a country does not automatically translate into their permanence in it.
In the case of Aquarius, for example, Spain announced that migrants would be interviewed one by one to know if they are susceptible to the protection and warned that those who are economic immigrants could be expelled.
"Taxi service"
Discussions among European states on how to manage the flow of migrants have been a constant for several years, largely as a result of the rules that require refugees to apply for recognition of that status in the first EU country. that they arrive.
This, argue Italy and Greece, meant that they had to take responsibility for the vast majority of those who arrived by sea.
For this reason, the Italian prime minister already announced that this week he will present in Brussels a proposal based on the fact that "who disembarks on the Italian, Spanish, Greek or Maltese coasts, disembarks in Europe", alluding to the responsibility of the bloc.
Italy, the destination of the majority of migrants from North Africa, requires EU sanctions for countries that refuse to accept a quota system such as the Visegrad Group – Poland, Hungary, the Czech Republic and Slovakia – which refuses to receive immigrants from other states.
Italian Interior Minister Matteo Salvini told the BBC that this type of vessel would never be admitted to the ports of his country and described the vessels operated by the NGOs as a "taxi service" for migrants.
Salvini criticizes the work of these organizations, on which he has already advanced, is considering taking measures to consider that they encourage the Libyan migrants to leave their country in an irregular manner by carrying out their boat rescues closer and closer to the coast.
In recent days, both Italy and Malta criticized Lifeline's vessel on the grounds that it "ignored the instructions" when it was instructed not to intervene in the rescue because the Libyan coastguards were going to be ordered.
Hungary, led by populist and Eurosceptic Prime Minister Viktor Orbán, took a big step in that direction by approving last week – on World Refugee Day – a package of measures criminalize and punish those who help immigrants with prison sentences irregular.
Source: BBC Mundo


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Pottery Painting & Ceramic Decoration
By "colour" we mean any product (typically a glaze or underglaze) that can be painted onto bisque, possbily glazed with a transparent over glaze and then fired to give a permanent ceramic finish. We include in this definition coloured and speciality glazes that can be painted onto bisque and fired in their own right to give a permanent ceramic finish.
There are a number of ready-mixed, vibrant colours or more subtle earthy tones with transclucent or opaque finishes. Most of the colours we supply are child-friendly, non-toxic and non-staining. Beware of other suppliers that sell glazes and underglazes with banned substances.
Our underglaze ranges are compatible with our bisque and clear glaze options (i.e. bisque fired to 1060°c or cone 04 with a recommended glaze fire of 1020°c or cone 06).
Our huge assortment of underglazes, glazes, specialty items and fired products will suit any budget no matter what your business - Ceramic Studios, Clay Cafes or Traditional Potters. Orders are typically despatched within 24-48 hours of receipt of order.


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July 31, 2015 Planning a website? How to get what you want from your web designer…
You're planning a new website and you have found a design agency or freelance designer that you want to work with. You have a good idea of what you'd like and the designer hopefully has plenty of design theory or natural ability stashed in their cranium. So how can you best make sure the designer produces something you will both be happy with?
Historically, you would give a designer a brief, and then (hoping that they've paid at least the slightest bit of attention, and not run off on their own personal design vision) they will then produce for you a set of designs that you will either like instantly, or, more often than not, iterate these in an attempt to make the design fit with your own personal vision. Unfortunately, this process could often end up with an unbalanced design that neither parties are happy with. Lengthy in time, as you are focusing 'end result, getting caught up the copy, site structure and that picture you don't like… The problem with this process is obvious, and can be solved by focusing on your brand feel and identity first.
Sadly we're hardly ever in a position to spend weeks pondering on colours, fonts, photography, textures and what they communicate to the general public, but that doesn't mean you should miss this stage out altogether, after all the websites that have seriously considered their brand are usually the ones we aspire to.
The good news is that there is an easy and cost effective way to create your look and feel, whilst taking control of the design process that in my experience, turned into a rewarding, collaborative and often vastly more creative process, which can be managed by either you or your designer.
A collaborative process
The best place to start is a short discussion with your designer/s about your business and who will be using the website. Keep this brief and high level. It might pay for you (or the designer) to create some basic customer personas, which can help keep a project focused (…I will blog about these soon).
The next stage is to create an inspiration board (see previous post), which helps you communicate your taste and what you think is suitable for your audience to the designer. The designer should also add his ideas to the inspiration board, and you should allocate a hour or so to talk these ideas through.
Following the inspiration board, you should ask your designer to produce a series of Style Tiles. Style tiling is a process being adopted by more and more designers as a creative tool and an ideal way to collaborate with the website project owners. In brief, and you can read more about the process on the Style Tile website, style tiling breaks the design process down into baby steps. The designer looks at the inspiration board and starts to think about fonts, colours and visual components at a basic level, then puts these ideas in a pre-made template and then presents these for discussion. If these concepts are liked, then a copy of the tile is made, and more detail is added, if not then another iteration is created at the same level of fidelity. Each iteration should have no more than a couple of hours design time spent on it, and the focus should be on collaboration and creativity at every stage. You must never think of the tile as an actual webpage or add real copy as these considerations are always a distraction. In my experience, the process takes around 3-5 days, and at the end you will have most of the components you need to build you site.
Added benefits of Style Tiling
I have been using this method for over a year, and because of the combination of inspiration boards and style tiles I have produced some of my best work ever, as it unlocks those creative blocks and prevents me from producing generic work. The process has vastly improved my relationship with my clients as it creates a common design language between us. There is never any design jargon or egos, we work together and create something new, which everyone can be happy with.
As you are designing components and not webpages, this process really suits responsive design as what you produce can easily be adapted to suit either media, and mobile components can be included into the final style tiles.
Finally, the processes saves so much time, compared to the cost in time and resources of producing whole finished webpages and iterating them one complete. .
The only tricky bit I can think of
As I mentioned before, this process requires very short iterations and ideally at least two meetings a day in order for it to move quickly. It can be done over longer periods, but many of us do our best work when we get our heads into a project and give it our full attention. Also, at first it is hard to lose that desire to design whole pages with real content, after-all this is a different mindset. Just stick with it, even if you end up moving into a full page design process, time spent on style tiling always pays dividends in my experience.
What next?
There should be no need to create whole pages designs, just more components as and when they're needed (maybe with the exception of the homepage). Page structures should be done in wireframe only, using pen and paper of wireframe software such as Gliffy. If you want to test your site on users, than that is a slightly different story. If you have a good wed developer to hand, then I am starting to favour using WordPress to make site mockups, which feel more real and often faster than just creating linked visuals…
Good luck with your designs and let me know how you get on.
Why not give me a follow on Twitter @oneplusone where I will let you know when I have published new blogs.


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Specialized in the sale of perfumes for several years, we have expanded our field with the design of an e-commerce site.
Our perfume essences are rigorously selected and come from the French laboratories of Grasse, world capital of perfume from which all the biggest brands are supplied.
We therefore guarantee a quality olfactory product with good hold on the skin.


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Durham, NC – December 27, 2012 – Biker Pros, the producer of the J&P Ultimate Builder Custom Bike Show, announced today that Indian Larry Motorcycles are participating in the New York round of the series and will be providing three Kustom Kulture bikes for the showcase on January 18-20. The showcase is a non-competitive class, which highlights dealers, manufacturers or builders that have unique or historic motorcycles.
Bobby & Elisa Seeger are holding the flame of Indian Larry in Brooklyn, NY and his brand of inspired Choppers and Bobbers from the 50′s-60′s motorcycle clubs, Ed "Big Daddy Roth" and the legendary Von Dutch. They will be debuting one new rolling metal-sculptor masterpiece along with two original Kustom Choppas. Continue reading "The NY Round of the J&P Ultimate Builder Features Indian Larry Motorcycles"


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If one of your New Year's Resolutions was to give your garden a bit more TLC, then getting your children involved will be a step in the right direction.
Sure your garden is a valuable play space, but if you want it to be more than a playground, your children will need to be a part of planting and caring for the flowers or vegetables you want to grow.
Here are some gardening ideas for February that all the family can contribute to:
1. Make A Note For The First Signs Of Life Every year when you get a new calendar, you mark out important anniversaries and birthdays. For children these dates help them mark time throughout the year, but can seem a long time apart, and are a little abstract to understand. Use your garden to fill the calender with dates of events for which they will have first hand experience. If it snows, write down when and how much. In February you can also look for the first signs of snowdrops breaking through the soil.
2. Sow Hardy Vegetables Broad beans, spinach, shallots and early carrots can all be sown outside at this time of year, with some protection against late frosts. Children can help sow seeds, erect protective coverings, and create labels so they don't get forgotten about.
3. Weeding And Clearing As the weather warms up, any weeds will burst into life, so now is a good time to evict them, long before they take over. Use this opportunity to explain to your children why some plants aren't good for the garden, but that they must only remove plants with your supervision.
4. Feed The Birds If you aren't doing it already, put some food out for the birds, who will be short on reserves as we reach the end of Winter. Children can make a simple feeder by rolling an empty cardboard tube in peanut butter, then covering with bird seed. Once you start feeding birds in your garden, you need to continue to do so regularly, as they will become reliant on you for food. Take care to hang the feeder away from play equipment to avoid it getting covered in mess.
5. Check Play Equipment Is Safe To Play On If you haven't done so already, carry out a thorough inspection of your outdoor play equipment. The worst of the winter weather should be over by now, during which your play equipment has ensured high speed gusts and low temperatures. Follow this guide for inspecting play equipment to check it's in a safe condition to be played on.
6. Clear Debris With the worst of the storms behind us, now is a good time to clear away the sticks and leaves littering the garden. Use the larger sticks stacked in a corner of the garden to create a bug hotel. Some leaves can be incorporated into your new bug home and the rest can be used in a compost heap.
Tempting though it may be to tackle these jobs alone, in the long run it is better to get the children involved in the garden Learning how to take care of their outdoor play spaces will help them respect the garden, and equip them with life skills they will need in later life.


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Welcome to The Joint Chiropractic - West Valley City! As your West Valley City chiropractor dedicated to family chiropractic and spine health, we invite you to join the millions of Americans who have not only found relief from lower back pain, sciatica pain, and migraines, but also a pathway to wellness with chiropractic's natural, drug-free approach to healthcare.
Whether you have seen a chiropractor in the past or are seeking a local chiropractor near you for the first time, expect your visit to The Joint Chiropractic - West Valley City to be different from any healthcare experience you've had before. Perhaps even life-changing.
Here are a few reasons why The Joint Chiropractic in West Valley City is your perfect destination for pain relief and preventative care:
As you can see, chiropractic care provided by the licensed chiropractors at The Joint offers you and your family an affordable, convenient and accessible solution like no other.
Through manual manipulation of the spine delivered to the highest standards by licensed chiropractors, chiropractic care works to restore and maintain proper communication from your brain to your body by relieving what chiropractors refer to as a subluxation, or a misalignment, of the spine. Restoring proper alignment to the spine can assist with pain relief and prevention of:
So whatever "symptoms" you or your family may be experiencing, visit our West Valley City chiropractic office today to learn more about how you could improve your overall health and well-being. And remember, you never need an appointment to visit, so stop in when it is convenient for you. We look forward to seeing you soon!
Dr. Quinten Madsen was raised in Ephraim, Utah and attended school at Snow College in Ephraim, Utah. He then continued his education at Logan University in St. Louis Missouri where he received his Bachelor of Life Science in 2014 and his Doctor of Chiropractic in August of 2015.
Upon his graduation, Dr. Madsen moved back to Salt Lake City, Utah and started working in a bi-lingual Spanish/English clinic in West Valley. He joined The Joint Chiropractic team in June 2018 where he strives to help others live happier, healthier lives and to improve their quality of life.
Throughout his professional journey, Dr. Madsen has learned to treat a wide variety of patients and symptoms including headaches/migraines, neck/mid/low back pain, sciatica, and arthritis. He does this by using a variety of adjusting styles and techniques.
In his free time Dr. Madsen enjoys the outdoors, hiking and camping. He also enjoys cooking and spending time with family and friends. When asked what brought Dr. Madsen back to Utah after graduation he said, "being close to family and the mountains."
Dr. Vickie Robert was born in a small town in California into a railroad family. This allowed her to grow up all over the US but she calls Kansas home. After working as a pharmacy technician in Kansas City for almost 14 years she decided that she wanted to pursue chiropractic in order to help more people achieve their health goals.
She attended Cleveland University- Kansas City where she studied for her Bachelors in Human Biology at the same time as her Doctorate in Chiropractic. She graduated with both degrees in 2018 and moved to Colorado where her husband had been working during the last two years of her education.
While living in a small town near Vail, Colorado she opened her own practice focusing on family wellness. "It was such a great experience to be able to see patients of all ages and help them to better be able to do all the activities that Colorado is known for."
In February of 2019 Dr Robert's husband's career brought them to Utah. She loves that she can see the beauty of the mountains without having to drive the narrow roads in the winter. "Utahans are such a friendly bunch of people. It really makes me feel like this is home." She's always looking for the best fishing spots and welcomes suggestions. She currently lives with her husband, two dogs, and a couple of chickens in the southern Salt Lake valley.
Read what our amazing chiropractic patients have to say about our chiropractors and care at The Joint Chiropractic - West Valley City in West Valley City, UT
In a recent Consumer Reports study, chiropractic outperformed prescription medication, deep-tissue massage, yoga, pilates, and over-the-counter medication therapies, in treating back pain. 1
1 Consumer Reports Health Ratings Center. Back-Pain Treatments. ConsumerReports.org; July 2011.
Recent health articles on chiropractic, lower back pain, neck pain, migraines, preventative care, healthy living and more.
Recent news, media appearances and press from around our network of 500+ chiropractic clinics.
Offer valued at $39. Valid for new patients only. See clinic for chiropractor(s)' name and license info. Clinics managed and/or owned by franchisee or Prof. Corps. Restrictions may apply to Medicare eligible patients. Individual results may vary.


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Keep your pets safe with the latest in pet tracking technology. Check the location of your pet at any time with the built-in app and set up a "GeoFence" so you can be instantly notified if your cat leaves a certain area such as your house, yard or street.
Real-Time GPS Tracker & History Tracker: Check the location of your pet at any time with the real-time GPS tracker. You can also track their entire history and see where they've been.
GeoFence Technology: Setup a virtual GeoFence around your house, yard or street and get notified instantly when your pet moves outside this area. Always have peace of mind knowing that your pet is safe and close to home.
Durable, Waterproof & Longlife Battery: The PetLove Cat & Dog GPS Tracking Collar is completely waterproof and extremely durable, so it will continue to track even if your pet has been in the rain or swimming.
We truly believe we make some of the most innovative products in the world, and we want to make sure we back that up with a risk-free ironclad 30 day guarantee.If you don't have a positive experience for ANY reason, we will do WHATEVER it takes to make sure you are 100% satisfied with your purchase.Buying items online can be a daunting task, so we want you to realize that there is absolute ZERO RISK in buying something and trying it out. If you don't like it, no hard feelings we'll make it right.We have 24/7/365 Ticket and Email Support. Please contact us if you need assistance.


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Expressions of interest are being sought from clubs who would like to host a round of the Irish Cross-country MTB National Point Series (NPS) in 2019.**The aim is to have five rounds.
Seven provisional dates have been identified for clubs to choose from.
Sunday 28 April 2019
Sunday 5 May 2019
Sunday 26 May 2019
Sunday 2 June 2019
Sunday 16 June 2019
Sunday 23 June 2019
Sunday 7 July 2019
The National Championships is a set date which is Sunday 21 July 2019 and we need a club to host this event as well.
A full calendar showing all disciplines is given*here.
Click*here*to download an Expression of Interest form.* This is to be sent to
email@example.com.* Closing date of applications is close of play Monday 26 November 2018.
Note: Clubs do not need to have secured confirmation from the landowner to submit an expression of interest.* *At this stage we are just trying to gauge interest from clubs willing to host events.


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Item Number
Product Name
Double Springs Heavy Duty Floor Spring
Maximum opening angle
Container Size
Maximum door width
Max Door Weight
130 kgs
Delivery Day
15-30 days
◪Applicable for glass doors,wooden doors,steel doors and the glass doors of metal frame and wooden frame.
◪Floor spring comply to EN1154 and ANSI standard,and fire-rated EN1634 standard.
◪Double ways opening with smoothly movement and noiseless,90°stop-device.
* Adjustbale Screws * CNC Head * Ajust Floor Spring Position * Brand New Iron Box
* Double Springs *Casting Iron Main Part * CNC Head * Two Speeds Adjustment
Built-in pressure relief valve protects the closer from rough use. Closer mechanism totally immersed in hydraulic fluid.
Use low temperature antifreeze hydraulic oil ,ensuring the normal door-closing speed when the temperature is fifty degree below zero degree.
Suitable for timber ,metal and tempered glass doors.
Over 500,000 cycles of circular testing, quality is ensured
Hello, please leave your name and email here before chat online so that we won't miss your message and contact you smoothly.


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5,500 miles, four land Rovers, six spare legs and an Allen key: How Britain's disabled war veterans took on the notorious Dakar Rally
Of the 450 vehicles that started the race in January, a third never made it to the finish. But this year one team faced even more of a challenge – a team of injured military veterans
Stage 1 of the 2013 Dakar Rally and team leader Captain Tony Harris is left stranded when the front differential breaks on his 4-litre V8-engined Wildcat
It's the most gruelling motorsport endurance race in the world.
The Dakar Rally is a 5,500-mile race over mountains and across deserts, often in stifling temperatures.
Of the 450 vehicles that started the race in January, a third never made it to the finish.
But this year one team faced even more of a challenge – the British Race2Recovery team of injured military veterans.
If you spend two weeks charging off-road over sand dunes and through flash floods, mechanical failures are inevitable.
But the Race2Recovery team had to cope with more than most. Their support vehicles were packed not just with spares for the team's four cars, but also replacement parts and an Allen key for running repairs on arms and legs.
'Everyone's body took a pounding driving up to 500 miles a day, but Tom (Neathway), as a triple amputee, had it particularly bad,' says team leader Captain Tony Harris, who is himself missing the lower part of his left leg after driving over an IED in Afghanistan in 2009.
'Tom has electronics in his prosthetic legs, and sand got into the pistons. There's a real camaraderie in the Dakar, though, and people help each other out.'
Major Matt O'Hare and Corporal Phillip Gillespie on the longest stage of the rally in Argentina
When the Dakar Rally started in 1978, it used to run from Paris to Dakar in Senegal. But after security concerns in Mauritania, the event moved to South America in 2009 and now runs south from Lima in Peru to Santiago in Chile.
One of the cars that finished was from Race2Recovery, the first ever disabled team to take part.
The four-litre V8-engined Wildcat, one of a team of four (the other three failed to finish), based on a Land Rover Defender, was driven by Major Matt O'Hare with co-driver Corporal Phillip Gillespie, a leg amputee following injuries sustained in Afghanistan.
Crossing the finishing line was the culmination of a two-and-a-half year plan for the 28-strong team of volunteers, funded by £1 million of corporate sponsorship from Land Rover, Bosch and Google.
That sum included £100,000 from the Royal Foundation Endeavour Fund founded by the Duke and Duchess of Cambridge and Prince Harry.
William sent congratulations via email to the team at the end of the event: 'What you have achieved was a triumph of perseverance and teamwork, and you have shown the world what true valour looks like.
'We hope you get some rest now and, please, no driving like that on our roads when you're back!'
Along the way they had to endure 15 days of sleep deprivation, crashes, fuelling problems, overheating, altitude sickness and broken prosthetics – as well as a tragic collision.
Corporal Tom Neathway and Corporal Tim Read relax between stages. Along the way they had to endure 15 days of sleep deprivation, crashes, fuelling problems, overheating, altitude sickness and broken prosthetics
Although they were all up for a challenge, you might think the British team, most of whom had suffered major injuries in Afghanistan, would not want to rush back to the desert sands.
'We overcame a lot of bad memories in Morocco, where we did some training with Land Rover,' explains Captain Tony Harris.
'There were moments there when we found ourselves driving past things that looked a lot like the compounds we'd driven past in Afghanistan. That was a bit unnerving to begin with.
'After that we were fine, and generally the guys are really happy in the desert, although for the above-the-knee amputees it's difficult to walk in the dunes because the sand shifts so much. But who doesn't like driving down them?
'One of the best moments for me was on the third day between Pisco and Nazca in Peru charging down a 700m-high sand dune towards the sea – it was just so liberating.'
The team's military experience certainly helped them cope when temperatures soared above 40°C, and with sleeping in pop-up tents on the desert floor.
'We've been in a lot worse places as soldiers, and the fact that we weren't being shot at was a great relief.
'As for the heat, once it gets over 40, who's counting? I remember it hitting 55 degrees in Iraq and we were in Warrior armoured vehicles then, which are basically just massive metal cans.'
The soaring temperatures did affect their cars, though, and it meant the British pair who finished the race had to drive many stages at night, to prevent their car overheating.
Corporal Tony Harris and co-driver Cathy Derousseaux at the start line in Lima
En route they each drank about eight or ten litres of water a day, and kept themselves going with energy bars and gels to supplement the uninspiring food provided by race organisers.
What was hard, though, was concentrating for such long periods and dealing with altitude sickness as they crossed the Andes twice, going up from 1,000m to just under 5,000m in a day.
The idea for Race2Recovery came to Captain Harris and Corporal Neathway in 2011, while they were both undergoing medical rehabilitation.
'The blast that injured me threw me 20 metres from the vehicle,' says Harris.
'I remember waking up on the desert floor, then the shock and adrenaline kicked in.
'Four years earlier in Basra in Iraq, I'd lost two fusiliers and two more of my soldiers had lost limbs on the same tour.
Tim Read cleans the windows of 'Joy', the only British car to make it to the finish
'As a platoon commander aged 24, that was the hardest thing I've ever had to deal with.
'When something happens to you, then you focus on how lucky you are either to be alive or not to have been injured worse. You can't just sit there and say, "What if?" Nothing good ever comes of that.'
The Dakar was far from an easy ride. His car had two bad mechanical days, and was then eliminated on day four for missing too many checkpoints.
But worst of all was what happened on day five, when tragedy struck.
One of Race2Recovery's support vehicles had a head-on collision with a local taxi.
Two people in the taxi died, and three British support team members had to be airlifted to hospital in Lima.
There were highs though, the biggest of which was crossing the finishing line.
'Little things stick in your mind, like the people with banners supporting us by the side of the road in Argentina.
'It was brilliant to see the human story transcending politics.
'Then there was the ex-French forces guy who'd been shot in Iraq, who I saw at the end of the race with a little tear in his eye just because the team had finished.'
So far the team has raised over £100,000 for the Tedworth House Personnel Recovery Centre in Wiltshire, where many of the team spent time recuperating from their injuries, but the hope is also to inspire others who are injured or disabled.
At the moment their focus is on veterans, but they are also proud to have helped a Belgian girl whom they met two years ago on Top Gear.
'She had lost both her legs to meningitis and was feeling pretty bad about life – she was only 18 or 19.
'She has met up with the team a couple of times since and she's now leading a full and active life and that's incredible.'
So is he now done with the challenge of the Dakar?
'My wife and two kids have been through the whole adventure with me and it was about putting the past behind us, so they'll have a say.
'But I'd love to go back – there's unfinished business between me and that race.'
'Race2Recovery: Beyond Injury, Achieving The Extraordinary' by Stephanie Temple is published by Haynes on March 14, £17.99.
£2 from every copy sold goes to Help For Heroes and the Race2Recovery Foundation. To order your copy call 0844 472 4157 or visit mailbookshop.co.uk
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Hey angels,
So my bank account officially hates me yet again, I only went and popped into boots didn't I!
If you didn't know already, I'm always on the lookout for good skin care and my colleague told me about the GlamGlow Tropical Cleanse Daily Exfoliating Cleanser and told me it was really good so I thought why not try it out for myself.
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- Superfruits – Help to gently polish the skin and remove impurities for a renewed glow, it also has a triple exfoliating blend of fruit extracts and pomegranate seeds and tropical fruit enzymes.
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I really like the consistency of this product, its definitely what you would expect from an exfoliating cleanser. Its quite gritty, which really feels like its getting the job done when you start rubbing it into your skin but its not harsh on your skin. I find it to be very refreshing when you rinse it off after and it really does make your skin feel super smooth and a healthy looking glow.
With most exfoliating products they normally say to not use them every day as its not very good for your skin but with this one it does say you can use it as an everyday cleanser, which to be honest, I still would probably only use this 2-3 times a week and use a normal cleanser on the other days.
Its only the second product I have tried of GlamGlow but I'm a huge fan and I will definitely be purchasing more items! I'm really keen to try there face masks so that will probably be next on the list!
Have any of you guys tried this product, if so then let me know in the comments what your thoughts are and if you have any recommendations for GlamGlow products then I'd love to know!
Thanks so much for reading guys and I'll speak to you all soon ♥


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Chroma-Q's Space Force Family Grows Even Stronger
February 7, 2020 09:00
North America, February 7, 2020 – Chroma-Q®, a world-renowned brand of premium performance LED lighting solutions, manufactured in North America, launched their new Space Force twobyfour™ LED soft light panel at BSC Expo 2020, Battersea Evolution, London earlier this month.
A scaled-up version of the onebytwo™, the twobyfour joins the award-winning Space Force family of bright, high quality, modern replacements for conventional sources used in film and TV studios, live broadcast, vlog, and photographic applications.
Like its more compact counterpart, it can be tuned from 2800K to 6000K with a superbly smooth intensity gradation, but in addition, up to 8 of its distinct cells can be controlled individually to create various shades or effects. The two soft light panels will be on show with the original Space Force LED space/soft light, which has been widely adopted by major Film & Television companies.
You will be able to find this fixture during NAB, Cine Gear, and Infocomm this spring. Get your personal demonstration of the range from Chroma-Q's North American Dealer, A.C. Lighting Inc. Alternately, please visit www.aclighting.com/space-force-twobyfour/ for more information and to schedule a demo. Check out our events page for complete details.
Follow Chroma-Q on: www.facebook.com/chromaq.lighting or www.instagram.com/chromaq
Chroma-Q and all associated product names are recognised trademarks, for more information visit www.chroma-q.com/trademarks. The rights and ownership of all trademarks are recognised. Whilst every effort has been made to ensure that the information is correct, Chroma-Q accepts no liability for errors or omissions. Technical specifications and data are provided for guidance only. Because we constantly aim to improve our products, we reserve the right to amend or alter at any time and without prior notice, the specifications of any product. E&OE.
About Chroma-Q
Chroma-Q® has been designing lighting equipment since the mid 1990s, when they established a reputation for high product quality, innovation and reliability with hugely successful products such as the Original colour changer.
In 2004 Chroma-Q launched their first LED fixture, the Color Block DB4™ - a product so popular that it's still selling today in a newer incarnation with upgraded technologies.
Since then, Chroma-Q have a gained a reputation for introducing award-winning, premium LED lighting solutions which deliver the highest performance levels required by today's most demanding applications - including concerts & theatre shows, film & TV broadcasts, retail, leisure & museum installations, exhibitions & corporate hospitality events.
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About A.C. Lighting, Inc.
A.C. Lighting, Inc. is a value-added distributor of world-class lighting and associated rigging technologies for the theater, film, television, worship, exhibition and commercial markets. A.C. Lighting Inc. is the exclusive North American distributor for premiere brands including Chroma-Q®LED lighting, Visa by Chroma-Q lighting and media control surfaces, PROLIGHTS high value and high-performance range of lighting, video and effects products, Luminex Networking Intelligence manufacturer of data distribution equipment, Follow-Me Remote Follow Spot Control Systems, LumenRadio wireless lighting controls, Jands StageCL and Prolyte staging and trussing.
For more information, please visit www.aclighting.com or call 416.255.9494
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Tuberous sclerosis complex (TSC) is a hamartoma syndrome in which brain, renal, and lung tumors develop and cause both morbidity and death. Loss of either TSC1 or TSC2 in TSC hamartomas leads to activation of mTORC1. Rapamycin and related drugs have been shown to have clinical benefit for these tumors in patients with TSC and those with sporadic forms of TSC-related neoplasms. However, lifelong therapy seems to be required, as tumors are not eliminated by this treatment. We examined the potential benefit of MLN0128, a novel potent mTOR ATP-competitive inhibitor, as a therapeutic strategy for renal cystadenomas that develop in A/J Tsc2+/− mice. Rapamycin given by intraperitoneal injection at 3 mg/kg 3 times per week, and MLN0128 given by gavage at 0.75 mg/kg 5 times per week had equivalent effects in suppressing tumor development during a 4-week treatment period, with an approximate 99% reduction in microscopic tumor cell volume. Marked reduction in activation of mTOR complex (mTORC)1 and blockade of cell growth was seen with both drugs, whereas only MLN0128 treatment had effects in blocking mTORC2 and 4EBP1 phosphorylation. However, when either drug was discontinued and mice were observed for two additional months, there was dramatic recovery of tumor growth, with extensive proliferation. Hence, longlasting tumor growth control is not achieved with transient treatment with either drug, and MLN0128 and rapamycin have equivalent therapeutic benefit in this mouse model. Differences in side-effect profiles might make MLN0128 more attractive for treatment of patients with TSC-related tumors, but will require additional study in humans. Mol Cancer Res; 11(5); 467–73. ©2013 AACR.
Tuberous sclerosis complex (TSC) is an autosomal dominant tumor suppressor gene syndrome, in which brain, kidney, and lung tumor development are major clinical problems (1, 2), and which is due to inactivating mutations in either TSC1 or TSC2 (3). Significant numbers of patients with TSC develop progressive brain subependymal giant cell astrocytoma (SEGA; ref. 4), renal angiomyolipoma (5), and/or pulmonary lymphangioleiomyomatosis (LAM; refs. 6, 7). All 3 of these tumors can be lifethreatening due to progressive disease development, and require therapeutic intervention. In addition, both renal angiomyolipoma and LAM are seen in patients who do not have TSC with similar clinical manifestations.
Tumor lesions in TSC have been shown to follow the classic 2-hit pathogenic model originally proposed by Knudsen for tumor suppressor gene syndromes (3). Patients with TSC have a germline mutation in either TSC1 or TSC2 (in the majority of cases), and show second hit loss of the remaining allele in their tumors. The TSC1/TSC2/TBC1D7 protein complex plays a critical role in the regulation of mTOR complex 1 (mTORC1), by acting as a GTPase-activating protein for RHEB, which functions to activate mTORC1 when loaded with GTP (8). Complete loss of either TSC1 or TSC2 inactivates the TSC1/TSC2/TBC1D7 leading to constitutive high-level activation of mTORC1 in TSC tumors (9, 10). Hence, drugs that inhibit mTORC1 have been logical candidates for therapeutic trials for TSC and related tumors.
Recent seminal studies have indeed reported that rapamycin (sirolimus) or related drugs, collectively termed rapalogues, have significant benefit for control of the growth of each of SEGAs, renal angiomyolipomas, and pulmonary LAM (11–14). However, despite the clinical benefit of these medications, there is considerable room for improvement in that lifelong treatment with the medications seems to be required for sustained benefit (11, 15). In addition, not all patients show clear evidence of response. For example, about 50% of patients with LAM fail to respond to sirolimus with continuing deterioration in their pulmonary function tests while on therapy (14). Although this may be due to indirect pathophysiologic effects that are independent of mTORC1 activation in LAM cells, it may reflect a direct therapeutic failure or limitation of rapalogue treatment. Rapalogues are allosteric modulators of mTORC1 function, acting through FKBP12, and although they affect mTORC1 at nanomolar concentrations, they do not affect phosphorylation of some downstream targets of mTORC1 such as 4EBP1 (16).
Genetically engineered mouse models of Tsc (17) have been available for some time, and although Tsc1+/− and Tsc2+/− mice do not have classic features of TSC, renal epithelial tumors develop and progress over a period of many months from pure cysts to cystadenomas with papillary extensions, solid adenomas, and at late ages renal carcinoma. The severity of these tumors varies a great deal among mouse strains, and is most severe in the A/J background (18). Many studies of rapalogues in Tsc mouse models have been conducted, always with dramatic clinical benefit. These drugs cause a approximately 99% reduction in microscopic tumor volume with a 1-month treatment period (19). However, similar to the experience in human TSC clinical trials of rapalogues, tumors recur when treatment is stopped.
Recently several compounds have been developed, which are mTOR ATP-competitive inhibitors, and have stronger, more complete inhibitory activity than rapalogues (20). MLN0128 is one such compound, which blocks the kinase activity of both mTORC1 and mTORC2, and which is in early clinical trials. MLN0128 has been shown, when combined with lapatinib, to result in antitumor activity in preclinical models of breast cancer resistant to anti-HER2 therapy (21). Here, we assess the benefit of treatment of cystadenomas in Tsc2+/− A/J strain mice with MLN0128 in comparison with rapamycin. We find that the 2 drugs have roughly equal benefit.
Materials and Methods
Ethics statement
All procedures were carried out in accordance with the Guide for the Humane Use and Care of Laboratory Animals, and the study was approved by the Animal Care and Use Committee of Children's Hospital (Boston, MA).
Mouse procedures
Tsc2+/− mice, originally generated in this laboratory (17), were serially crossed with A/J mice for over 5 generations. These pure strain mice were used in all experiments.
Standard histology and tumor assessment
Mouse kidneys were removed rapidly after euthanasia, and were fixed overnight in 10% formalin. Gross scoring of kidney tumor lesions was conducted by a single observer (Y. Guo). The gross tumor score for each kidney was determined as a summed score for all lesions in a kidney, scoring each individual tumor grossly as follows: 1 for tumors <1 mm; 2 for 1 to 1.5 mm; 5 for 1.5 to 2 mm; 10 for >2 mm (19). Kidneys were then prepared for histologic evaluation in a stereotypical fashion by cutting the kidney into sections at 1 mm intervals throughout its length.
Microscopic kidney tumor scores were determined in a semiquantitative fashion by a single blinded observer (Y. Guo). The set of 1 mm interval sections were prepared as hematoxylin and eosin (H&E)-stained 8 μm sections. Each tumor or cyst identified was measured to determine its length and width in 2 dimensions, as well as the percentage of the lumen filled by tumor (this was 0% for a simple cyst, and 100% for a completely filled, solid adenoma). These measurements were converted into a measurement of tumor volume per lesion using the following formula. Tumor volume = maximum (tumor percent, 5)/100 * 3.14159/6 * 1.64 * (tumor length * tumor width)**1.5 (19). The total tumor volume per kidney was then equal to the sum of the tumor volume of each lesion identified. Comparisons between sets of mice for tumor measurements were made using the nonparametric Mann–Whitney test in Prism (GraphPad Software, Inc., v4.0a).
Mouse livers were harvested for immunoblotting by rapid postmortem freezing in liquid nitrogen and were stored at −80ºC until further use. Lysates from those organs were prepared by standard methods (19). Protein concentrations were determined using the Bradford assay, and equal amounts were separated by electrophoresis on precast 4 to 12% Bis-Tris gels (Invitrogen) and transferred onto polyvinylidene difluoride membranes. The membranes were blocked with 5% nonfat dry milk in TBS-10% Triton-X for one hour at room temperature. Primary antibodies were diluted in 5% bovine standard albumin in PBS, 0.1% Tween20 (pH 7.4) serum, and were applied to the membranes for overnight incubation at 4ºC in a wet chamber. Antibodies used for Western blotting were as follows: Akt (Santa Cruz Biotechnology), pAKT(S473), pS6(S240/244), total S6, p4EBP1(S65), and total 4EBP1 (all from Cell Signaling Technology). After extensive washing, horseradish peroxidase (HRP)-conjugated secondary antibodies (Santa Cruz) were applied for 1 hour at room temperature. SuperSignal West Pico or West Femto (ThermoScientific) chemiluminescence reagents were used to detect antibody binding. Immunoreactive bands were detected by exposure to film (Denville Scientific)
Eight micrometer paraffin sections were deparaffinized with a xylene and alcohol series, treated with Target Retrieval Solution, pH 6.1, (Dako), blocked with 3% H2O2 in methanol, and then put in 5% normal goat serum in 0.1% Triton X in PBS. Sections were incubated with primary antibodies overnight at 4ºC, washed, and incubated with secondary antibody conjugated with HRP. 3,3′-diaminobenzidine chromogen solution (Envision+System Dako) was then applied to generate a color reaction. Slides were then counterstained with hematoxylin (Dako). Antibodies used for staining were: anti-pS6 (S235/236; 1:100, Cell Signaling, #2211). Proliferating cell nuclear antigen (PCNA) staining was done according to the protocol of HistoMouse-Plus kit (Invitrogen). Hematoxylin was used as a counterstain and an adjacent section was stained with H&E.
Drug handling and administration
Both drugs and vehicle were given to 2 cohorts of mice. In one cohort, the mice were treated for one month, from age 4 months to age 5 months, and then sacrificed for analysis at the end of treatment, age 5 months. In the second cohort, the mice were treated for one month, from age 4 months to age 5 months, treatment was discontinued, and the mice were observed out through age 7 months when they were sacrificed for analysis.
Rapamycin was purchased from LC laboratories. A 20 mg/mL stock was made using ethanol, and mixed daily for injection with sterile vehicle (0.25% PEG-200, 0.25% Tween-80). Mice were treated with rapamycin by intraperitoneal injection at 3 mg/kg 3 times per week for one month. Control mice received the vehicle solution intraperitoneally on the same schedule.
MLN0128 was provided by Intellikine, Inc. as a powder. It was dissolved in vehicle (5% 1-methyl-2-pyrrolidionone, 15% polyvinylpyrrolidone K30, and 80% water) and administered by gavage 5 days per week, on weekdays. The initial dose used was 1.0 mg/kg for the one-month treatment, 7 month end point cohort. In that cohort, 4 of 8 mice showed loss of 10% or more body weight after 4 to 9 days of treatment, and therapy was withheld for 5 to 10 days until weight returned to less than 10% weight loss, and then restarted at 0.75 mg/kg per dose. The second cohort treated was treated for one month, and then sacrificed at 5 months of age. Those 9 mice received 0.75 mg/kg from the beginning of their treatment, and none displayed weight loss of 10% or more body weight.
For short-term treatment studies, Tsc2+/− AJ strain mice of age 6 months were treated with rapamycin by injection, MLN0128 by gavage, or vehicle injection. They were then sacrificed for rapid collection of kidneys 6 hours later.
Results and Discussion
We explored the potential benefit of mTORC1 inhibition with rapamycin in comparison with the ATP-competitive mTOR inhibitor MLN0128 in A/J strain Tsc2+/− mice. Rapamycin was given by intraperitoneal injection at 3 mg/kg 3 days per week. MLN0128 was given at 1 mg/kg per os by gavage 5 days per week, and then reduced to 0.75 mg/kg when weight loss of 10% or more was seen in some treated mice (see Materials and Methods for details). Otherwise, both treatments were well tolerated. Rapamycin was highly effective in reducing the gross tumor score and microscopic tumor volume (Fig. 1A to C), similar to what we have seen previously (19). MLN0128 was also highly effective in reducing the gross tumor score and microscopic tumor volume in these mice (Fig. 1A to C). Both treatment regimens reduced the median microscopic tumor volume by about 99% (Fig. 1C), and comparisons of each of gross tumor score and microscopic tumor volume between drug- and vehicle-treated mice were highly significant. Consistent with this quantitative improvement, both drugs led to a significant difference in tumor histologic appearance (Fig. 2, left). For both drugs, the kidney lesions seen after treatment were mainly cysts, with a few containing some small papillary extensions into the cyst lumen. In contrast, solid adenoma lesions were seen in the vehicle-treated mice kidneys. Rapamycin seemed to have a slightly better effect in tumor control in these experiments, with a slightly lower gross score and microscopic tumor volume than MLN0128-treated mice (Fig. 1A and C). However, this was not statistically significant.
We also examined both the acute and long-term effects of drug treatment on mTORC1 activation and tumor growth rate in the kidney lesions of these mice (Figs. 3 and 4). Analysis of histologic sections of kidneys from A/J Tsc2+/− mice of age 6 months prepared 6 hours after a single treatment with either rapamycin or MLN0128 showed that both drugs eliminated phospho-S6(S235/236; pS6(S235/236) expression in the cystadenomas, and also eliminated PCNA expression (Fig. 3). Similarly, both drugs eliminated pS6(S235/236) and PCNA expression in A/J Tsc2+/− mice of age 5 months after 1 month of treatment (Fig. 4A). These observations indicate that the drugs were clearly affecting their intended targets in vivo, and blocked cell growth in the cystadenoma lesions. Examination of liver extracts from the 1-month treated mice showed that MLN0128 markedly reduced pAKT(S473) levels, as well as pS6(S240/244) and p4EBP1(S65) levels, consistent with effective mTOR blockade affecting both mTORC1 and mTORC2 targets (Fig. 5B; refs. 9, 10). In contrast, liver extracts from rapamycin-treated mice showed a reduction in pS6(S240/244) only with no change in pAKT(S473) or p4EBP1(S65), consistent with rapamycin's more limited activity in blocking mTORC1, and not affecting phosphorylation of 4EBP1 (16). Immunoblot analysis of Tsc2 MEF lysates showed the expected effects of MLN0128 treatment with marked reduction in both pS6(S240/244) and p4EBP1(S65), in contrast to rapamycin (Fig. 5A).
We also assessed whether rapamycin or MLN0128 treatments might provide long-term disease control after cessation of treatment. A/J Tsc2+/− mice of age 4 months were treated for one month until the age of 5 months, and were then taken off treatment for 2 months and sacrificed at the age of 7 months to assess tumor extent. Strikingly, the 1-month treated mice, either rapamycin or MLN0128, showed a sharp rebound in tumor growth off drug, such that the median tumor microscopic volume was about 40% of that of mice that received vehicle treatment only (Fig. 1D to F), or in other words, displayed an average approximately 60% tumor volume reduction. Nonetheless, there was a highly significant difference in microscopic tumor volume in each of rapamycin- and MLN0128-treated mice at the age of 7 months in comparison with vehicle-treated mice. Furthermore, there was no significant difference between the rapamycin- and MLN0128-treated mice in their microscopic tumor extent at age of 7 months. As the tumor microscopic volume measurements suggest, histologic assessment showed that there were many cystadenomas that had papillary tumor extensions as well as solid adenomas in the mice treated for one month with either rapamycin or MLN0128, and then followed up for 2 months off therapy (Fig. 2, right). The cystadenoma cells comprising these lesions showed robust expression of pS6(S235/236) indicative of mTORC1 activation and expression of PCNA, as expected (Fig. 4B). Liver extracts prepared from these mice also showed no difference in the pattern of mTOR phosphorylation events from vehicle-treated mice (Fig. 5B). Thus, collectively these data show that MLN0128 and rapamycin have similar effects in the dramatic control of Tsc2+/− mouse kidney cystadenomas, but the tumors recur at a rapid rate when the treatment is discontinued.
Tuberous sclerosis affects an estimated 40,000 individuals in the United States, and 10% to 20% of these individuals are expected to experience significant morbidity and/or mortality due to the development of tumors (1, 2). Fortunately, there has been major progress recently with the demonstration that sirolimus and everolimus are effective therapies for SEGA (13, 15), renal angiomyolipoma (11), and pulmonary LAM occurring either in TSC or as sporadic conditions (14). However, there are significant ongoing clinical issues with this therapeutic approach, including the apparent need for lifelong therapy (11, 15), and the lack of apparent benefit in about half of the patients with LAM treated with sirolimus (14).
The mouse model studied here replicates the relatively benign histologic appearance and slow progression of the tumors that develop in patients with TSC. We showed once again that rapamycin is a highly effective therapy for treatment of the renal cystadenomas that develop in Tsc2+/− mice, with an approximate 99% reduction in microscopic tumor volume seen with one month of treatment. Also similar to previous studies, we observed that these tumors recur vigorously when rapamycin is discontinued, similar to the observations made in patients with TSC when rapalogue therapy is discontinued (11, 15).
MLN0128 is a member of a new class of compounds that are ATP-competitive inhibitors of mTOR (20). We show that MLN0128 treatment has therapeutic benefit in this TSC mouse model that is essentially indistinguishable from the effects of rapamycin. Renal cystadenomas examined by immunohistochemistry and liver extracts examined by immunoblotting show that MLN0128 is effectively blocking the activity of both mTORC1 and mTORC2. Unfortunately, the Tsc2+/− renal cystadenomas show the same dramatic but transient response to MLN0128 treatment, with dramatic regrowth when therapy is discontinued. Thus, each of these mTOR inhibitors fails to provide long-lasting disease control when therapy is discontinued.
These 2 classes of drug have different mechanisms of action. Rapalogues act by binding to FKBP12 and allosterically modulate the kinase activity of mTORC1. They are highly effective in blocking S6 kinase and its downstream effects, but have limited and variable effects on 4EBP1 phosphorylation (as shown here, Fig. 5; ref. 16), and do not directly inhibit mTORC2. Furthermore, rapalogues have complex effects on T helper cells and dendritic cells leading to immunosuppression (22), which is an undesirable side-effect of their use for patients with TSC-related tumors. The effects of ATP-competitive inhibitors of mTOR, such as MLN0128, on immune function are currently poorly studied. It is possible that their lack of interaction with FKBP12 will lead to reduced immune function effects in comparison with rapalogues. In addition, MLN0128 has effects on 4EBP1 phosphorylation and AKT phosphorylation at S473, both in vitro and in vivo as shown here (Fig. 5). These effects might lead to greater benefit than rapamycin in patients with TSC-related tumors.
Thus, the current work indicates that rapamycin and MLN0128 have equivalent effects in controlling tumor growth in this mouse model of TSC. Although this equivalence would tend to diminish enthusiasm for trials of ATP-competitive mTOR inhibitors in patients with TSC, it is possible that the side-effect profile of MLN0128 and related drugs might be milder or different from that of rapalogues especially with respect to immune system function while providing therapeutic equivalence. Further investigation will be required to explore this possibility.
Disclosure of Potential Conflicts of Interest
D.J. Kwiatkowski has a commercial research grant from Intellikine, Inc. and is a consultant/advisory board member of Millenium. No conflicts of interest were disclosed by the other author.
Authors' Contributions
Conception and design: Y. Guo, D.J. Kwiatkowski
Development of methodology: Y. Guo, D.J. Kwiatkowski
Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): Y. Guo, D.J. Kwiatkowski
Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational
analysis): Y. Guo, D.J. Kwiatkowski
Writing, review, and/or revision of the manuscript: Y. Guo, D.J. Kwiatkowski
Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): D.J. Kwiatkowski
Study supervision: D.J. Kwiatkowski
Grant Support
This work was partially supported by Intellikine, Inc., now a wholly owned subsidiary of Millennium Pharmaceuticals, Inc., and by NIH NCI 1P01CA120964.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The authors thank I. Malinowska for advice on immunohistochemistry and tumor scoring techniques.
- Received October 19, 2012.
- Revision received December 21, 2012.
- Accepted January 7, 2013.
- ©2013 American Association for Cancer Research.


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Soul on Soul: The Life and Music of Mary Lou Williams
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Book Summary:
Book DescriptionPianist, composer, and arranger, Mary Lou Williams (1910?1981), was one of the most significant and influential artists in the history of jazz. A versatile musical genius who experimented with and mastered most of the emerging styles in jazz's evolution, Williams wrote and arranged for such greats as Duke Ellington and Benny Goodman, and she was friend, mentor, and teacher to the likes of Thelonious Monk, Charlie Parker, and Dizzy Gillespie. Yet throughout her prolific career of nearly six decades, she battled as an African American woman to achieve recognition, equality, and acceptance in the male-dominated world of jazz. Now Williams's artistic brilliance and lasting legacy are affirmed in this definitive volume, which masterfully interweaves biographical details with incisive commentary on her music, performances, and recordings. Setting Williams's intriguing story against the racial, social, cultural, and musical currents of her times, Tammy L. Kernodle...
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Book DescriptionGrowing up in the rural town of Alexandria, Indiana, Bill Gaither dreamed of becoming a gospel singer. He set out to do just that during his college years and after much frustration, ended up teaching high school English. It was hardly the life he had hoped for. From this humble ...
Janie Harris. Elegant Soul: The Life And Music Of Gene Harris
Book DescriptionGene Harris was a musician?s musician. Whether it was through his work with the famed jazz trio The Three Sounds or in his role as the leader of the Philip Morris Super Band, Gene Harris carved an indelible place for himself in the annals of American jazz music. A contemporary ...


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- Men's SEIKO 6309-7049 For PARTS or REPAIR -- Not Running
Men's SEIKO 6309-7049 For PARTS or REPAIR -- Not Running
per item
I bought this because I planned to get it up and running, but never did. I love the creamy patina on the indices and hands. It doesn't run and needs to be repaired or used for parts. The crown screws down with about 3 turns, the date turns over as it should. The bezel spins somewhat freely, perhaps just lacking a gasket? See pictures for best description.
International buyers, shipping may be more than the standard $13. Please email me for a quote before purchasing.
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These adorable ash gray mules are just what you need as the perfect neutral shoe this season! They are so comfy and easily slip on, perfect for the woman on the go! The chunky heel makes them so easy to walk in! We love the cut out design showing the perfect touch of foot. These will match almost anything so be sure to make them yours today!
- Heel Height: 3"
- Color may vary on different viewing devices.


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As impressed as I was with the 2010 Emmy nominees, there were (of course) a couple of omissions I take serious umbrage with. And clearly I'm not alone — that pic above captures the exact moment nominee announcer Sofia Vergara learned she had been nominated and nominee announcer Joel McHale learned he had not.
Outstanding Guest Actor in a Drama
Zach Gilford, "Friday Night Lights"
A quiet storm was always brewing within Matt Saracen and when his father was killed in Iraq, actor Zach Gilford really brought the thunder. The journey he took Matt on in 44 minutes rivals what most actors can do with a full length feature film. What's even more shocking is the episode, titled "The Son," snagged an Outstanding Writing nomination. Um, guys, who do you think infused those words with such emotional weight?
Outstanding Supporting Actor, Comedy
Ed O'Neill, "Modern Family"
Shockingly the Pritchett patriarch ended up being the only adult from "Modern Family" to miss out on a supporting actor nomination. Perhaps Jay's subtler comedy was overshadowed by the showier scenes and scenarios his co-stars get.
Best Comedy, Best Actress, Best Supporting Actress
"Cougar Town" was repeatedly robbed. Courteney Cox has never been better while Busy Philips is pure week-in/week-out hilarity. The writing is sharp, the characters are unexpected and the show is clearly being eclipsed by timeslot partner "Modern Family."
Best Supporting Actress, Comedy
Merritt Wever, "Nurse Jackie"
Much like the hospital they work at, Jackie Peyton is only as good as her support staff — and Edie Falco could never be as amazing as she is without back-up from supporting players like Eve Best, Peter Facinelli and most importantly Merritt Wever. Her Nurse Zoe is the most dependable bright spot on the whole series and could carry a spin-off should Jackie's pill popping ever push her over the edge.
Outstanding Choreography
Travis Wall, "So You Think You Can Dance"
How this Jason Mraz-accompanied contemporary routine was overlooked is beyond me. This piece not only set Jeanine up to win season five, but established Travis as one of the most original, affecting and inspiring choreographers on the show.
What was the biggest snub?
Photo: AP Photo; NBC; FOX; ABC; Showtime


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Wearable devices are becoming part of our daily lives, tracking our exercise, sleep and calories. But who is tracking these devices and their accuracy? How can we respect people's privacy while collecting data? And how can we use the collected information to have a real, positive effect on our wellbeing? Our multidisciplinary team with experts in medicine, health, physical sciences and engineering will answer these questions to find real-world solutions.
We compare the data collected by wearable devices (activity, sleep, step count) with measurement conducted in laboratories to study their efficacy. We also focus on building effective databases to store the information while respecting people's privacy. We also study how to provide tailored feedback back to the public, so that they can improve their health and wellbeing.
Our main areas of study are sleep, physical activity, and periods of inactivity.
We seek to use wearable devices to provide solutions to real-world problems. Smart watches and fitness trackers can help researchers collect data in a more sustainable way and to understand lifestyle patterns that lead to chronic disease. Devices have the potential to provide live feedback to users and educate them to prevent those diseases. We aim to connect researchers, health professionals and community to obtain measurable health benefits.


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– one of Johannesburg's many overlooked water sources.
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Judith writes: There exists a tiresome myth that the city of Johannesburg was not built on a river. No human being would build away from water, which is a first requirement for life.
The truth is that Johannesburg was built on many rivers and not one single one. Of these, the Sandspruit is but one. It flows north as do the Jukskei, the Braamfontein Spruit and many other lesser streams, all of which end up in the Crocodile River. On the south side of the ridge of White Waters is the Klip river and many others such as the Wonderfonteinspruit.
What all our rivers have in common today is pollution and neglect. Everything is put into them, from plastic bottles and bags to sewerage. Their fragile banks are lined with invasive plants and developers, who do not understand flood lines and the need for respecting water runoff from heavy rain storms. Their ignorance results in deaths –human and animal– as flash floods sweep all before them. More urgently, but so far unseen, is the penalty that we are paying for this concretization of our environment and destruction of grasslands. We are bringing on the great thirst as water can no longer reach the water table under the earth by simply sinking away into it as before.
We have lost the understanding of our relationship with nature and believe that we can dominate it. We are not nature's masters and never will be: We were intended to be its shepherds and guardians –look at anyone's religious text and you will find that that was what was intended.
The fact that these texts were written when humanity was closer to nature than we are today demonstrates the fact.
As urbanites, many of us believe that everything comes from the supermarket, that the supply of food is handled – by whom, I am not sure. However, it is inexhaustible and we can always rely on it. Ask a few friends in the rural areas for their take on this!
Now to return to the Sandspruit, whose banks are not always accessible, even though they are supposed to be and whose special residents do care about the life in and around the river.
It is the northern residents from Kelvin Drive to South Road and a little beyond who do care. There are lapses, and King David School could do a whole lot more and use the river as an education in biology, botany and chemistry. In fact, all the local schools should be using the river in their education programmes. Contact me for ideas!
Beyond that, we have some of the most beautiful walking spaces on our rivers – why are we not preparing them for the visitors for the Confederation Cup and 2010? Or even our visitors now? Many people enjoy walks in riverine areas and many visitors love hiking. We are missing a funding opportunity by neglecting our river trails and one which can come directly from tourists.
To illustrate this, here are some photos taken on our various walks on the Sandspruit:
Just something to suggest you come on our walks on Sundays to see the river and everything around it.
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For your ultimate combination of awesome Desert Canyons and the very best bits of California, take a look at our Wild Wild West Tour. If you have less that 16 days available, no worries ride the separate sections. And we've a special offer on Spectacular California for 2019!
Kick stands up on Wild Wild West
5 – 20 Sept 2019
Kick stands up on Desert Canyons and Historic Route 66
5 – 12 Sept 2019
Kick stands up on Spectacular California
12 – 20 Sept 2019 – FREE PRE-TOUR NIGHT IN VEGAS


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T'Preth was a female Vulcan in the 21st century, and was the helm officer under Commander T'Lera during their ill-fated observational mission to Earth in 2045. She was noted for her calm and soft-spoken manner, even in the face of disaster, and was also an accomplished linguist and artist. T'Preth was consort to Stell, the mission's sociologist, and both perished together as the vessel fell into Earth's atmosphere. (TOS novel: Strangers from the Sky)
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Many Anglican women came out in their numbers to protest against their Bishop after accusing him of marrying more than one wife and looting. A shocking incident paralyzed activities on Sunday as members of the Anglican Church Boyo Road, Sapele staged a peaceful protest against Bishop Erifeta over corruption, abuse of public fund and marrying two wives.
The protesters mostly women using placards called the Bishop many names and accused him of different offences. They appealed to Primate Okoh to remove the Bishop of Sapele Anglican over the allegations leveled against him.
Here are more photos shared by Sapele Oghenek on Facebook about the incident:


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Payment Card Interchange Fee and Merchant Discount Antitrust Litigation
The merchant plaintiffs in In re Payment Card Interchange Fee and Merchant Discount Antitrust Litigation, MDL No. 1720 (MKB)(JO), have asked a federal court in Brooklyn to approve their landmark class action settlement.
Robbins Geller attorneys, serving as co-lead counsel on behalf of merchants, have reached a $6.26 billion cash settlement with defendants in this antitrust litigation. Defendants have contributed additional funds to the class settlement fund that remains from the earlier settlement in 2012, which was approved by the district court in 2013 but was then reversed on appeal in 2016. The case was preliminarily approved on January 24, 2019. The final approval hearing is scheduled for November 7, 2019.