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On Friday, the Royals gathered for the wedding of Princess Eugenie and Jack Brooksbank.
Of course, among the guests were Prince William and wife Kate. And while waiting for the bride they proved they’re still as loved-up as ever.
The Duke and Duchess of Cambridge showed some rare PDA. They looked so adorable holding hands while sitting down next to Harry and Meghan.
William held on to Kate’s hand which she placed on his knee as she caught up with Harry.
William also put his hand tenderly across his wife’s back as they exited the chapel.
But, it is necessary to say that Eugenie and Jack’s wedding wasn’t another working engagement. It was a family event which explains why the couple was more open to showing affection.
Still, if they hold hands at a working engagement, they wouldn’t be breaking rules.
“There is no actual etiquette or royal protocol that says the couple must refrain from PDA,” Myka Meier, a royal etiquette expert and founder and director of Beaumont Etiquette, told People in 2016.
The rare PDA from William and Kate is the second one we’ve seen this week. William affectionately touched Kate’s back as they arrived at an engagement at the Global Ministerial Mental Health Summit on Tuesday.
When it comes to Harry and Meghan, they continued to show their affection by arriving in the Chapel holding hands.
For the wedding, Meghan opted for a demure navy Givenchy dress. She completed her look with a pair of navy shoes and a matching navy hat by Noel Stewart.


text:
By the firelight, a mysterious storyteller weaves a captivating tale of sea journeys, vampire women, and Aboriginal Dreaming. Around the campfire the gold diggers listen and journey with George as he plunges underground to rescue his ship's captain from the horrific and mesmerising vampire woman.
Jangamuttuk, the Master of the Ghost Dreaming, sends his son, George, to rescue Wadawaka from the 'ghost' vampire woman who has taken him as her 'Dark Lord' and imprisoned him in her underground kingdom. Will George, in either his human form or as his Dreaming animal-self Dingo, be able to withstand Amelia's powers; will he survive the underground caverns; can he tear Wadawaka and himself from the violent but seductive power of the vampire woman? And who is the strange but familiar ghost woman accompanying the new colonial governor?
Underground is the 3rd in the Master of The Ghost Dreaming quartet, beautifully and insistently portrays the enduring reality of Aboriginal Dreaming in a fascinating story of initiation, maternal longing, and colonial violence.

industry_corpus2: Film & Entertainment


text:
When the sun goes down, many families wrap up their fun for the day, but wait ’til you see what can heat up after dark!
Suit up for a family game of 3D Laser Tag. Test your driving skills when you take a fast ride around the go-kart track. Play in the MEGA arcade, take a swing at the batting cages or enjoy the kiddie rides. You may want to take a nap because this place is open until midnight on Friday and Saturday nights.
Get a bird’s-eye view of Central Florida when you take off into the wild blue yonder on an unforgettable aerial tour. For nighttime fun, choose either a sunset or fireworks aerial tour and see your favorite theme parks in a new light – and from new heights. This is really a special evening that's perfect for a date night too!
Make your own light show when you paddle through Mosquito Lagoon at the Merritt Island National Wildlife Refuge – at night. It’s a phenomenon called bioluminescence, where light is produced naturally from living organisms like jellyfish and bacteria. Movement against the water causes the water to glow, so when you paddle, glowing streaks appear!
Play mini golf in the moonlight. Test your skills in the arcade. Race to victory on go-karts. This place has so much going on, you won’t slow down for a moment. With its thrilling rides, bowling, bumper boats, a rock climbing wall and more, you can definitely get your game on at Boomers.
Feed a giraffe for breakfast – after you’ve spent the night sleeping next to the tigers! Your kids will love exploring the park after dark, and the experience will provide years of bedtime stories. All sleepovers include a pizza snack, continental breakfast and hands-on educational activities.
This gives all new meaning to camping in the wild! Bring your sleeping bag and you can doze off next to turtles, manatees, dolphins, beluga whales and other interesting creatures! You’ll get to do all kinds of fun and educational activities. Plus, you know the kids will love having pizza for dinner. Breakfast is included, too.
Your heart will definitely be beating fast as you step off that first platform to soar in the darkness! Over the pines, under the moonlight – it’s exhilarating! Kids 10 and older (and adults!) are welcome to zip in the dark at speeds up to 30 mph. Moonlight zips are held most Saturday nights.
Watch the dazzling fireworks over Cinderella’s Castle from a pontoon boat in the Seven Seas Lagoon, but first, enjoy a swashbuckling reception at Walt Disney World’s Contemporary Resort. This is fun for all ages and you’ll get a souvenir bandana, autographs with Captain Hook and Mr. Smee as well as other surprises!

industry_corpus2: Travel & Geography


text:
López Lambas, María Eugenia and Ricci, Stefano (2014). Planning and management of mobility in natural protected areas. In: "XVIII Congreso Panamericano de Ingeniería de Tránsito, Transporte y Logística (PANAM 2014)", 11/06/2014-13/06/2014, Santander, España. ISBN 978-84-617-0085-1.
The final purpose is the identification of: a) the effects of various choices in transport planning, both at long term and strategic level; b) the most effective policies of mobility management. The preliminary work was articulated in the following steps: 1) definition of protected area on the basis of ecological and socio-economic criteria and legislative constraints; 2) analysis of mobility needs in the protected areas; 3) reconstruction of the state of the art of mobility management in natural parks at European level; 4) analysis of used traffic flows measurement methods; 5) analysis of environmental impacts due to transport systems modelling (limited to air pollution and noise); 6) identification of mitigation measures to the potentially applied. The whole methodology has been firstly tested on the case study of the National Park of ?Gran Sasso and Monti della Laga? and further validated on the National Park of ?Gargano?, both located Italy: i) the concerned area has been zoned according to the land-use peculiarities; ii) the local situations of transport infrastructure (roads and parking), services (public transport systems) and rules (traffic regulations) have been mapped with references to physical and functional attributes; iii) the mobility, both systematic and touristic, has been synthetically represented in an origin-destination matrix. By means of an assignment model it has been determined the distribution of flows and the corresponding average speeds to quantify gaseous and noise emissions. On this basis the environmental criticalities in the reference scenario have been highlighted, as well as some alternative scenarios including both operational and infrastructural measures have been identified. The comparison between the projects and the reference scenario allowed the quantification of the effects (variation of emissions) for each scenario and a selection of the most effective management actions to be taken.

industry_corpus2: Transportation


text:
When I try to enter a formula, (i.e. Match() function, Sumif(), and other functions) where the parameter points to range on another sheet, locking reference using Shift+F4 sometimes not responds.
I must edit the formula manually add the $ symbol.
Shift+ F4 does not work when the link is to a different Calc file. In this case I need to add the $ signs manually.
Sample formula: =A1 - press SHIFT+F4 it appears: =$A$1 (locks row and column) - press SHIFT+F4 again: =A$1 (locks row) - press SHIFT+F4 again: =$A1 (locks column) - press SHIFT+F4 again: =A1 (back to default no locking).

industry_corpus2: Programming


text: This was another project done in collaboration with Hi-ReS! London. The j12 Moonphase iPad app is an in-store sales aid made specifically for demonstrating the advanced features of the j12 Moonphase watch line. Unfortunately the app is not available on the AppStore but you can watch a demo of the features.

industry_corpus2: Computing & Telecommunications


text:
MrTuRkIsH, by.root and Âlfonse like this.
MrTuRkIsH, Âlfonse and KocaReis like this.
MrTuRkIsH, by.root, KocaReis and 1 other person like this.

industry_corpus2: Others


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We will work with you to create your floral dreams. We want your wedding to be as perfect as you do. We will work closely with you to create bespoke floral designs to capture your personality and relationship, and to truly encapsulate your special day. We understand that every detail counts.
As flowers are our passion we can work with you to design flowers to suit any theme. Our team of experienced designers will work closely with you from consultation to final delivery to provide you with bouquets, button holes, centrepieces, flower crowns, floral archways or floral installations.
From the very conception, to the liaising with the venue and suppliers, right up to the final installation, we will work with you to create floral displays you’ve always dreamed about.
We will book a personalised wedding consult with you, either in our Paddington tea room, or if you are planning from afar we are happy to email, Skype, Facetime or carrier pigeon plan your wedding flowers.


text: Tips: Garply.com is the most dynamic, highest-quality information among the U.S. Yellow Pages information site, owns a million times visits per day. Garply.com can help people use the easiest way to find and release Averill information. As find phone:802-822-5583 or YPHCCode:May 1203963, you can browse info about 'Stein Harold' freely in Garply.com.Welcome to www.garply.com again!


text: Description: In late 1992, Alittle Voodoo began playing all over western Canada. By 1993 they recorded their first live CD over three rockin\' nights in Banff\'s Legendary club the Rose and Crown. In 1994, Alittle Voodoo began touring with blues/rock acts: Colin James, the late Jeff Healey, The Headstones, Paul Rodgers, Long John Baldry, David Gogo, Omar and the Howlers, Bo Diddley and a host of others. Alittle Voodoo is led by frontman and guitar mauler, Ron Burke. Likened to Stevie Ray Vaughn, Johnny Winters, and a few others. Ron’s barrelhouse vocals partnered with his steamroller guitar playing won’t let you believe you are hearing a 3 piece band. In 1994, the band was recognized with Best Band of the Year, with Ron also taking the honours as Best Male Vocalist and Best Guitar Player at the CJ92 awards.


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Jim told us a fascinating story from about 10 years ago.
A successful Toronto Business woman in her mid 40’s died. When cleaning out her Harbourfront condo a mummified baby was found in a garbage bag in her storage area. Before her death, the mother indicated she had an adopted 15 year old daughter and friends were to be the daughter’s guardians.
Jim’s department investigated the mummified body. It was determined the baby died within 24 hours of birth. DNA proved that the deceased woman was the mother of the baby.
She had been treated for bladder cancer for more than 7 years so the baby was born prior to that. The baby was wearing a baby shirt and diaper. The diaper manufacturer (Huggies) was contacted to help determine when the baby died. Huggies advised that the diaper was last manufactured in 1984.
The investigators determined that the woman had a male companion at that time who now lived in England. He was contacted and admitted to having a sexual affair with the woman - his DNA was also a match. Thus the parentage of the mummified baby was resolved.
An interesting twist to the story was that the guardians of the adopted daughter, contacted Jim’s area because they could find no record (birth certificate, adoption records, OHIP number etc.) of the girl. On further checking DNA proved the deceased woman was also her mother. Although the mother indicated the girl had been homeschooled, there was no record of this. The girl was articulate and seemed educated. She said everything she knew she had learned from The Learning and Discovery Channels. When she entered the school system, she was in the 90th percentile within 3 months. She went onto university and is now doing Ph. D in Psychology. It was never determined who her father was but she inherited her mother’s $5,000,000 estate and she has established contact with her mother’s family.


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The primary mission of the DMD Genetic Therapy Group at the Department of Human Genetics of the Leiden University Medical Center is the development of a genetic therapy for Duchenne muscular dystrophy (DMD). The project started in 1998 and is currently supervised by Prof. Dr. Annemieke Aartsma-Rus, after Dr. Judith C.T. van Deutekom left in February 2007 to work as Head of research for the biotech company Prosensa B.V. (Leiden, the Netherlands). In a joint effort the DMD Genetic Therapy Group and BioMarin (previously Prosensa) are developing antisense oligonucleotides (AONs) as small synthetic molecule drugs for DMD.
The DMD Genetic Therapy group also studies muscle pathology in dystrophic cell and animal model systems, ways to improve muscle quality, the identification and validation of biomarkers and the processing of the dystrophin transcripts.
The DMD Genetic Therapy Group was awarded for its research by the Princess Beatrix Fund in 2001 and by the LUMC (C.J. Kok Award) in 2003.
We hope you find all the information you are looking for on this webpage. If not please do not hesitate to contact us by using the contact form.
For Parents of Duchenne Muscular Dystrophy patients we have created a special website (in Dutch and English), written in a non-scientific language. Please have a look and let us know if you miss information.
Recently a new video has been created to show a “bit more behind the scene footage” of our work here in Leiden and tells a bit more about exon skipping and the DMD disease.
Duplications are challenging for the mutation specific type of approaches (exon skipping). However, there are other appraoches in development.
what can i do if i want exon skipping….
i am suffering from dmd….
Exon skipping is an approach that aims to slow down disease progression. Muscle function that is lost will not return.
It is also a mutation specific appraoch. Not all mutations are suitable unfortunately.
Dear Annemieke , today i heard the last part of an interview with you on Radio1 about the influence of mobile phones on the well-being of youngsters. What survey or news item did this refer to? Would you also think that such devices have an impact on persons at their workplace? As i am interested in how advanced automation and robotisation will impact the life of people on the workplace.
My interest is therefore both professional and private.
Thank you in advance for your response.
The problem with mobile phones and tablets is that they produce a lot of light – especially in the blue spectrum. This is not harmful in itself. The problem is that blue light interferes with the production of melatonin. Melatonin is a substance your body makes that helps you sleep. It needs to accumulate for about 3 hours before there is enough to get you to sleep easily. So if you use tablets or mobiles in the evening, melatonin can not accumulate due to the blue light exposure. This can lead to difficulties falling asleep.
So it is not the mobile phones that are harmful, but the lack of sleep if you use them until very late.
Hi, we’re desperately trying to find out how to get exon skipping for TJ. He’s a three year old boy who has just been diagnosed. We’ve just started raising funds to help us in our endeavour. However we have no idea where to start in terms of having access to the treatment or how much money we need or even when he might be eligible for the treatment. Please, please help us? Any information on who to contact or how to start on this journey would mean the world to us! Thank you so much for taking the time to read this. I hope to hear from you soon. Warm regards Mrs Jennifer Batterbee.
What is TJ’s mutation? Not all mutations are suitable for exon skipping.
Het is niet mogelijk om dit middel te gebruiken – het is namelijk niet een medicijn want nog niet goedgekeurd. De ontwikkeling van de “Biomarin/Prosensa” exon skip middelen is gestopt omdat de bijwerkingen niet opwogen tegen de zeer beperkte effecten in een klein groepje patienten.
In Amerika is afgelopen week een ander exon skip middel goedgekeurd (Eteplirsen, van het bedrijf Sarepta). In Europa wil Sarepta ook exon 53 middelen testen.
Good care is very important to keep Duchenne patients as functional as possible for as long as possible.
The exon skipping approach probably will not apply to your son. The approach aims to restore the genetic code. However, a deletion of exon 45-53 does not disrupt the genetic code (so therefore it cannot be restored). For this mutation we would expect a milder progression (Becker) – However, there are exceptions, e.g. it is possible that while on DNA level the genetic code seems not to be disrupted, it IS disrupted in the temporary RNA copy because parts of the gene that are important for gene processing are missing. Since the protein is translated from this RNA copy (and not directly from DNA), the way the RNA copy looks like, is what determines whether protein can be produced. However, RNA and protein analysis can only be done on muscle tissue. How was the mutation found? Only by DNA analysis? Or was protein analyzed as well?
I have son with DMD and we recive genetic test which shows c.3151C>T in exon 23coresponding to the mutation p.Arg.1051.
What these mean? Can he take some terapy?
I am sorry to hear about your son.
The mutation you describe is a so called nonsense mutation (also called stop mutation). Genes contain the genetic code for proteins. Each gene has a start and a stop signal so the translation machine knows where to start translating the gene into protein and when the protein is finished. For most Duchenne patients part of the genetic code is lost (deleted) and therefore the code becomes unreadable, so it is not translated. However, for some patients, like your son, there is a very small change that changes the code for a part of the protein into a stop signal. This means that translations is stopped prematurely and no functional protein is produced.
There is a therapy that addresses this type of mutations. It is called stop codon readthrough and the drug that achieves this is called Ataluren (tradename Translarna). Ataluren is approved for treatment of ambulant Duchenne patients 5 years and older in Europe by the European Medicines Agency. It is on the market in several countries in Europe. In addition there are access programmes for patients outside Europe. It is a treatment, not a cure. It does not stop the disease, but slows down its progression.
Thank You very much for Your qucik replay. Can You tell me which clinic in Europa I can contact and go with my son. Ina our country, Bosnia, we do not have good doctors. Nobody tell as about this tretman. They do not know abou it. If You have some contacts please send me. Thank You very much.
My nephew is suffering from Dmd duplication of Gene 57 to 60 what does duplication means is the prognosis same as deletion.
I am sorry to hear about your nephew. The dystrophin gene has 79 exons. A deletion means that part of the gene is missing (e.g. exon 57-60). A duplication means that part of the gene is ‘doubled’, in case of your nephew he has exon 1-60, but then instead of exon 61, he has an extra copy of exon 57, 58, 59, and 60, and only then exon 61-79. The consequence of deletions and duplications can be two-fold: 1. They can disrupt the genetic code. This means that dystrophin protein cannot be produced and patients have Duchenne. 2. They can maintain the genetic code, allowing the production of a dystrophin that is slightly shorter but has its functional domains. These proteins are partially functional and are found in Becker patients (less severe disease).
A duplication of exon 57-60 is unfortunately of the type that disrupts the genetic code. So you would expect him to have the severe type of the disease. There are exceptions to this rule however, so it is not possible to say this with 100% certainty.
My son is 4 years old and has exon deletion from 48 – 52 . How feasible is an exon 53 skipping and i have read that trial results are due only in 2019 . What other treatments can be done in the mean time ?
Exon 53 skipping is indeed tested in clinical trials at the moment. As yet we do not know whether it is effective or safe (of course we all hope it is both effective and safe, but the trial is done to evaluate this).
What can be done already is provide good care to your son to keep him in as good a condition as possible for when hopefully a therapy is available. More information on care guidelines for Duchenne can be found here: http://www.dmd-guide.org/. This is based on two scientific papers published on this topic, but ‘translated’ into more accessible language non medically trained individuals.
Referring to deletion exon 48 -52 my son was diagnosed based on DNA Results .
Can you explain please the difference as part of symptoms and progression of the disorder would it slow or fast.
is milder or sever !
A deletion of exon 48-52 unfortunately disrupts the genetic code of the dystrophin gene. That means your son cannot produce functional dystrophin and he would be expected to have Duchenne muscular dystrophy – the more progressive form of the disease.
Here you will see that there are approaches in development that apply to all Duchenne patients regardless of their mutation. In addition there are mutation specific therapies in development. The latter have been developed furthest and two compounds have been approved: Translarna (in Europe) and Eteplirsen (in the USA). Translarna only applies to nonsense mutations – so the child you mention would not be eligible since he has a frame-shift. Eteplirsen is an exon 51 skipping compound, aiming to restore the reading frame. However, this would also not work for the child you mention since exon 51 is deleted already. Exon 53 skipping would restore the reading frame for this patient. Exon 53 skipping compounds developed by Sarepta therapeutics are in clinical development in the USA and Europe. To my knowledge no trial is currently going on in India, but I know DART (Duchenne Annihilation Research Trust, located in Bangalore) is preparing clinical trials in India.
My Son is 7-years, Muscle Biopsy says consistent with DMD but MLPA ( Genetic Test ) reveals point mutation at 46 chromosome.
I am sorry to hear your son has DMD. The mutation you describe however, does not make sense to me. Do you mean a deletion or duplication of exon 46? A small mutation in exon 46? Feel free to email me privately if you prefer (you can find my email address on publications). I will need this information to provide information about mutation specific appraoches.
Very good to hear your son is doing physiotherapy – good care is the most important thing you can do for him!
Mijn zoontje is 19 maanden en heeft Duchenne, hij heeft deletie 51. Kan hij met deze deletie in aanmerking komen voor exon skipping of is dit niet voor deletie 51 van toepassing?
Exon skipping is een mutatie specifieke aanpak waarbij gepoogd wordt om Duchenne patienten een deels functioneel dystrofine eiwit te laten maken in plaats van een niet functioneel eiwit. Hiervoor moet tijdens het verwerkingsproces van gen naar eiwit dus een exon geskipt worden. WELK exon hangt af van de locatie van de mutatie. Een exon 51 deletie komt in theorie in aanmerking voor deze aanpak. Om de leesbaarheid van het gen te herstellen moet exon 52 OF exon 50 worden geskipt. Momenteel wordt er geen klinisch onderzoek gedaan met middelen om deze exonen te skippen. De focus ligt vooral op het skippen van exon 51, 45 en 53 momenteel omdat dit toepasbaar is op de grootste groep patienten.
My grandson is 7 years old and was diagnosed as having DMD ( most probably )due to duplication of exons 53 to 57 .He is ambulatory and does physiotherapy is specialized center . we give him Tamoxifen 10 mg daily for 1.5 months now . He is doing better since then . What is your comment on the duplication regarding prognosis and treatment . Also ,if you have any comments on Tamoxifen ( I know that it is in clinical trial but I took the risk because I cannot wait till I see him helpless and not moving so early ) .
I am sorry to hear about your grandson. Good care is really the best thing that can be doen for him – this means physiotherapy but also has other aspects (see http://www.treat-nmd.eu/care/dmd/family-guide/). I cannot comment on tamoxifen other than that it is a therapy that has yet to be tested in Duchenne patients. It has yet to be shown that this drug is effective and that it is safe in Duchenne patients. The fact that it works in mice is no guarantee that it will work in patients. The fact that it appears to be safe in mice is no guarantee that it will be safe in Duchenne patients.
Regarding the duplication: it is expected to disrupt the genetic code of the dystrophin gene and as such is a “Duchenne type” of mutation. The milder disease course of Becker is expected for mutations that do NOT disrupt the genetic code. However, how your grandson will progress exactly is difficult to predict since every patient is unique. This will depend on how well his muscle regenerates, how well his immune system works, how muscular he is to begin with etc.
Coming back to the start: the best thing to do is to make sure he has good care – this is the best way to slow down the breakdown of muscle as much as possible.
The question is the said mutation disrupted the whole function of the gene or only the site beyond or below the mutation site(exons)in other words the gene is functioning till Exon 52 only that can translate the proteins before the duplicated exons or not functioning at all?
Another question if the site (region) of mutation in specific area of the gene differs in severity than other parts of the gene even if disrupt the reading frame for example if I have 2 patients,1 with duplication of Exon 18-22 (out of frame) and the other patient has duplication of Exon 53-57 ( out of frame also) do both of them have the same severity or not?
I am sorry to hear your son has Duchenne. I will try to explain some of the genetics to you – hopefully this will answer your questions.
Duchenne is caused by a failure of patients to produce a functional dystrophin protein. The dystrophin protein fulfills a linker function in the muscle. One side of it connects to the skeleton/internal structure of the muscle fiber, the other size connects to the connective tissue surrounding the muscle fiber. In between there is a spring like system consisting of 24 similar domains. The connection stabilizes muscle fibers upon contraction.
Duchenne patients have a mutation that disrupts the genetic code of the dystrophin gene (out-of-frame mutations). Consequently, the code becomes unreadable after the mutation. Because the important domains of dystrophin are located at the start and the end of the protein, the resulting dystrophin will not be functional. It will lack the domain that connects to the connective tissue. As such it does not matter whether the mutation is at the start or in the middle are even close to the end – the crucial domain at the end will be missing and therefore the dystrophin is not functional.
In fact, the part in the middle of dystrophin is redundant. We know this because in-frame mutations affecting the middle of the protein keep the genetic code readable. As such dystrophins can be produced that have the important domains at the start and the end, but are shorter in the middle. These proteins are found in the less severe Becker muscular dystrophy.
In summary, for out of frame mutations it does not matter where the mutation is located – if the domain at the end of the protein (encoded by exons 64-70) cannot be produced, the protein will not be functional. As such they will both cause Duchenne.
Please do not hesitate to ask for clarification if this is not clear to you or ask follow up questions.
First:is there any trials currently recruting regarding the mentioned mutation for my son(duplication 53-57)?
Third: which is better “Prednisone or deflazacort” noting that our neourlogist has recommended Prednisone 15 mg/d in addition to multivitamins,but we didn’t start steroids yet?
Fourth:she recommended swimming 1hr a week but didn’t recommended physiotherapy right now?
Last question:shall we start using night splint and hand braces for him now or later?,also shall we delay steroids or start now?
There are no clinical trials ongoing specifically targeting your son’s mutation. However, there are multiple trials ongoing for which mutation type is not an issue. See for an overview: http://www.treat-nmd.eu/dmd/research-overview/introduction/. The mutation specific approaches currently under evaluation (exon skipping and nonsense codon readthrough) will not apply to your son’s mutation. However, approaches aiming to reduce fibrosis, improve regeneration, decrease inflammation will apply to all DMD patients.
Could you please tell me what is the difference between non sense (stop codon) mutation and large duplication that alter the reading frame like my son’s case,as i know that both disrupt the reading frame but do both have the same severity phenotype? And different propability of the total absence of the dystrophin protein?
A nonsense mutation does not disrupt the reading frame. It changes the genetic code at one position so that the code reads “stop” rather than genetic information. These stop codes are normally only present at the end of the genetic code, so the translation machinery knows the protein is complete. When a mutation changes the genetic code into a stop earlier in the gene, the translation stops too early and the protein is not functional. So the consequence is the same as with frame-shifting mutations (translation stops too early and protein is not functional). As such, these nonsense mutations cause DMD, like the frame shifting mutations.
The MLPA results suggest there is deletion of exon 48 to 52 of the DMD gene at hemozygous state. However this test will not detect any alteration that lie outside the target probe sequence.The deletion within the DMD gene results in frame-shift and therefore premature dystrophin , which agrees with the DMD diseases. diagnosis.
The MLPA will test for each part of the genetic code of the dystrophin genes (the so called exons) whether they are present or not. In case of your son, exons 48, 49, 50, 51 and 52 are missing. This disrupts the genetic code, so starting at exon 53 this becomes unreadable for the machinery that translates gene to protein. He therefore cannot produce functional dystrophin.
Exon skipping aims to restore the genetic code by making the deletion one exon larger. In case of your son’s mutation, exon 53 skipping would restore the genetic code. Exon 51 skipping will not work because your son does not have exon 51, so it cannot be skipped.
I’ve sent you an email about the twin boys of a friend of mine. Is there a clinic you work in The Netherlands? By any chance can we contact you for an appointment? Please, my friend is desperate specially becouse in the city he lives in Brazil doctors know very little about it.
I am not a medical doctor so I cannot see your friend’s sons. I will email you about options in Brazil.
That would extremely helpfull!!! Thanks a lot!!! Looking forward to your e-mail.
My son has a single base deletion in exon 56 (c.8375delA). Is exon skipping working with such small deletions. Which exon needs to be skipped to restore a truncated dystrophin for him?
2. While the larger deletions that remove one or more exons are clustering in the area of exon 45-55, small mutations (like the one of your son) occur in all exons. This means that exon skipping for small mutations applies to very small groups of patients (less than 0.1% of all patients generally).
So exon skipping as it is currently in development for DMD will not be applicable to your son, unfortunately. However, all the mutation independent approaches in development (anti-fibrosis, anti-inflammation, pro-regeneration, mini-dystrophin, utrophin upregulation etc) do apply.
Thank you very much for this explanation.
Hello, the 5 year old son of our very good friends has just been diagnosed with DMD with duplications of Exon 6 and 7. We live in Turkey and I wondered if you could give us any information on clinical trials or treatment options available in this country?
Also, if they were able to travel would there be any other trials you could recommend?
I am sorry to hear about your friends’ son. Note that Turkey has a very good Duchenne specialist, Dr. Haluk Topaloglu and that he is involved in multiple clinical trials. I do not know by heart which ones are currently happening and whether your friends’ son would be eligible to participate, but I am sure his team will be able to inform you about that.
Note that participation in clinical trials is a burden. Clinical trials are experiments in humans. There is no guarantee that the test drug will work and they may be unsafe. Also trials generally mean many hospital visits – so this in and of itself is a burden as well. It is best to participate in a trial that is local – this reduces the travel burden for the patient and the family (e.g. weekly hospital visits are more rule than exception) and trials may be daunting to the patient, especially when he is young and when the trial is in another country where they speak a different language. So when possible I would recommend a local trial.
Genome editing (using CRISPR/Cas9) can in theory correct both deletions and duplications. For deletions, the aim is to restore the genetic code, while for duplications, the aim is to restore the normal code. This can be achieved by cutting out the duplicated parts. However, this work is as yet in a very early stage and only tested in patient-derived cell cultures. So there are no clinical trials ongoing specifically for duplications at the moment.
Note that all therapies that are not mutation specific would apply to all patients (so also patients with duplications).
My 6 months grandson was found to be missing exon 46-47. We were told it is Duchenne. Is there any chance this could change as he gets older? What about skipping therapy?
I am sorry to hear about your grandson. For a deletion of exon 46-47 indeed Duchenne muscular dystrophy is expected, because this mutation disrupts the genetic code. There are sometimes exceptions (i.e. patients who have a milder progression than anticipated), but unfortunately these are few.
Hi, I would like to ask which mutation (deletion, duplication and point) is/are not suitable for exon skipping and why?
The dystrophin that is produced after exon skipping needs to have all its functional domains.
The dystrophin has one dystroglycan binding domain encoded by exon 64-70. This is absolutely crucial. So if a mutation is located/includes exon 64-70, exon skipping will not result in functional dystrophins. This goes for all types of mutations (deletions, small mutations and duplications). With deletions parts are missing, while with duplications parts are double. However, the extra parts of dystrophin can affect the folding of the protein, so that while they are present, they are not functionally active.
The dystrophin has 3 actin binding domains, two encoded by exons 2-10 and one encoded by exon 32-45. To be functional dystrophin needs at least one actin-binding domain. So mutations that remove all three are not eligible for exon skipping, since the resulting dystrophin will not be functional. Note that the first two actin binding domains are “better binders” than the third one. So a dystrophin that lacks the first two domains is less functional (associated generally with more severe Becker) than a dystrophin lacking the third actin binding domain (associated with typical Becker). For small mutations (point mutations) it is not possible to affect all three domains – only for large deletions and duplications this can be an issue. With deletions parts are missing, while with duplications parts are double. However, the extra parts of dystrophin can affect the folding of the protein, so that while they are present, they are not functionally active.
The dystrophin has a connecting domain that is encoded by exons 11-63. This domain is largely dispensable. However, when deletions are longer than 36 exons, the domain probably becomes too short. For duplications it is not known how large they can be and still result in a functional protein. For small mutations of course the exons deleted after exon skipping will never involve more than 36 exons.
My son is 5 years old and gene 49, 50, 51 and 52 are delete, I would like to know more about possible treatment and institutes where I can contact for cure of his DMD illness, I really need guidance please help.
Unfortunately there is no cure yet for DMD – not anywhere in the world.
There is good care which can help slow down the progression of the disease – you can find out more about this here: http://www.treat-nmd.eu/care/dmd/diagnosis-management-DMD/ It is important to find a hospital with experience in caring for Duchenne patients so that your son can receive the care he needs.
Also there are therapies in development and two therapies have been approved now. However, these are mutation specific and your son is not eligible for those. He would be eligible for “exon 53 skipping”, which is tested in clinical trials. This means that as yet we do not know whether this appraoch is safe and/or effective. Also know that the therapies currently in development are unfortunately not cures – they aim to slow down the progression of the disease.
I am sorry I cannot give you more positive news. Know that there are many people world wide who work hard to find a better therapy for Duchenne, but that this is challenging.
My son have Exons 45,46 and 47 are deleted. He is 32 months old now,we don’t see any notable symptoms so far. He is ahead to reach his motor skills like crowling and walking.
When he tested for jaundice last year due to some other illness his liver enzymes were elevated and they see liver was normal so they started testing ck and genetic testing.
His doctor is saying RNA analysis is needed to confirm whether this is mild and severe type though it’s a inframe mutation.
We are so scared what will be the outcome of RNA tests.
Can you please help to confirm is this kind of mutation happened to anyone already ( Exons 45,46 and 47 deleted) and what will be the type of their disease whether it’s mild or severe.please help.
Sorry to hear your son has a mutation in his dystrophin gene, but glad to hear he has no notable symptoms so far.
For mutations that are in-frame, one would expect the milder disease (Becker) rather than the severe disease (Duchenne). Note that RNA analysis requires a muscle biopsy – which is a painful and invasive procedure. As such, this is only recommended when the symptoms do not match the genetics (e.g. in-frame with severe symptoms or out-of-frame with mild symptoms). This does happen sometimes (in about 10% of cases) and the mutation you describe has been found in Becker patients but also in some Duchenne patients.
When the symptoms match the genetics (90% of cases), the international guidelines for Duchenne diagnosis, care and management (see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869704/figure/F2/ – from this paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869704/) do not recommend RNA analysis.
So I recommend that you ask the doctor why (s)he thinks RNA is needed. Is the disease more severe than expected for a Becker patient? If so, then the analysis makes sense. However, if your son does not have the typical Duchenne symptoms, I do not think the RNA analysis is needed.
Doctor mentioned it’s a blood test for RNA analysis not the muscle biopsy.
They say in particular in frame deletions (like my son’s) needs RNA analysis to confirm whether it’s a Becker or Duchene.
Does CK elevation (as it was around 30k ) matters to confirm Becker Vs Duchenne.
CK elevation means there is something wrong with the muscle – in case of muscular dystrophy the muscular dystrophy is ‘what is wrong’ and why the enzyme leaks from the muscle into the blood. The elevation points to a problem with muscles, but it does not tell you which problem there is (i.e. which protein is missing or not only partially functional) – this is why the genetic tests are needed. One cannot say which muscular dystrophy a person has based on how high the CK levels are because CK levels also vary due to e.g. time of day, how active you have been and how muscular you are etc.
RNA analysis in the blood will not be informative at all. Dystrophin is not expressed in the blood, which will make the analysis very challenging and has the risk of misinterpretation. The guidelines (internationally recognized, published in The Lancet) say that DNA analysis by MLPA is sufficient for deletions involving multiple exons. There is never a need for RNA analysis in the blood (because this is not informative) – if the symptoms do not match the genetics, RNA anlaysis can be done on muscle.
I had a discussion with doctor and currently hold on RNA analysis. We have in person appointment scheduled for next week to talk more on this.
Earlier you mentioned exon 45-47 deletion shows in both Becker and Duchenne.
Without RNA analysis what decides the disease is mild (Becker) or severe (Duchenne), is it symptoms? or based on the age symptoms occurs?
can you please give more details like in Duchenne at which age age typically symptoms start and is developmental growth (motor skills) is always delayed with this case.
And with Becker what will be the symptoms and usually at which age symptoms start.
The severity of the disease is determined by the symptoms and when they occur. Duchenne is the more severe form, and symptoms occur already early in life, at around the age of 1-3 years old. Patients e.g. will have difficulty with walking, hopping/jumping, climbing stairs and will fall frequently already before the age of 4 years.
For Becker there is a lot more variation in when the disease starts – in some patients this is in childhood, in some patients this is in adolescence or even adulthood. So here it is not possible to give a specific age – it varies – even when several patients are affected in the same family, when the symptoms start and how severe they are can differ between the patients.
Note that I am NOT a medical doctor – what I write about the symptoms is what I know from the literature and what I have heard from clinicians treating Duchenne and Becker patients.
Hello my son who is 3 yr old has been diagnosed with duplication of exon from 8 to 11 of the DMD gene, is there any cure or medicine in the pipiline to correct this dysfunction of exons?
im a father of a 7 years old boy, he have DMD because of exon2 duplication’, is any solution available today to solve this kind of mutation.
At the moment there is no cure for Duchenne. There are therapies in development that aim to slow down disease progression. This is done by one in 2 ways: 1) trying to restore the missing protein 2) trying to improve the muscle quality.
Restoring dystrophin is often done in a mutation specific way. For an exon 2 duplication, exon 2 skipping would restore the genetic code of the dystrophin gene. At the moment this is not tested in clinical trials, but Kevin Flannigan is doing preclinical tests to assess exon 2 skipping in cell and mouse models.
What is the anticipated prognosis for a duplication of exons 52 and 53?
A duplication of exon 52 and exon 53 would be expected to maintain the reading frame. So in theory one would expect this mutation to be associated with Becker muscular dystrophy. However, duplication mutations often have unpredictable impacts on how the gene transcripts are processed and a significant number of duplication mutations that do not disrupt the readin frame result in Duchenne, and vice versa duplication mutations that disrupt the reading frame can also result in Becker muscular dystrophy.
So the ‘prediciton’ is a lot less reliable than with deletion mutations.
Thank you very much for your prompt response, I think I have the child well on track because he is enrolled precisely with Kevin Flanigan at the Ohio hospital, where he is working on the subject, what worries me is that he is alone with his team watching this issue of exon 2 duplication.
Anyway, I thank you for your attention and I am happy to know that there are still good people in this world who try by all means to make happy the families that suffer for their children.
Can you kindly guide how can we determine whether a point mutation in DMD gene is in frame or out of frame mutation? and if a particular nonsense mutation can be corrected by ataluren.
I would be grateful if you can provide me literature on the recent mutation spectrum of Duchenne worldwide and the diagnostic methods and therapies available so far.
All nonsense mutations should be correctable by ataluren. Whether a point mutation is in-frame or out of frame depends on how many basepairs are involved (a basepair is a DNA building block). If there is a deletion or insertion of basepairs: if the number is divisible by 3 (e.g. deletion of 6 basepairs or insertion of 3 basepairs) the mutation is in-frame. If it is not divisible by 3 (e.g. deletion of 5 basepairs or insertion of 1 basepair), it is out-of-frame. A nonsense mutation does NOT disrupt the reading frame – however, because the code for an amino acid is changed into a STOP code, it leads to truncation of translation of the code from gene to protein and therefore a non functional protein. So the effect is the same (out-of-frame mutations also lead to a premature truncation of translation, but for a different reason – the code becomes unreadable).
Exon skipping for duplications is challenging. What would be required in case of your sons is skipping of either the first exon 44 OR the second exon 44. Either way would restore the normal dystrophin code. HOWEVER, the compounds used for exon skipping (antisense oligonucleotides, AONs) recognize both exons 44 – so there is a possibility that both exons will be skipped. This would disrupt the genetic code (just like the exon 44 duplication does).
If we test AONs for exon 44 skipping in cultured cells of a patient with an exon 44 duplication, what we see is that both exons are skipped. So this is not helpful. It is possible however that when patient would be treated this would not be the case. For both exons to be skipped you need 2 AONs in the same cell (one to bind the first exon 44 and one to the second exon 44). In cultured cells this is easy to achieve (the cells receive an overdose of AONs so to say). However, in a human being the amount of AONs is much lower and as such it is anticipated that most cells will have no AON at all, and some will have 1 AON and hardly any with have 2 AONs. Therefore it is expected that in a patient, this would work better than in cells and that there might be some dystrophin restoration expected. However, exon skipping has so far never been tested in patients, so there is no hard evidence yet.
At the moment there are no exon 44 skipping compounds in clinical development, so for now this is unfortunately only theoretical.
I am a father of child with exon 55 deletion reported in DNA Blood test.
2. My kid is 5.6 yrs and is able to walk and play. only difficulty with him is stair climbing now.
3. He is on put on Steroid 20mg, after a month having this medicines his face changed to moon one.
Pl. pl. support my child to live a normal life with and strength to overcome this.
I am sorry to hear about your son’s condition.
With regards to your questions: Steroids unfortunately have side effects (such as the moon face) – however, they are slowing down the disease a lot. They allow patients to walk longer and have a better respiratory function and better survival among others.
MLPA: when a deletion of one exon is found with MLPA, a second test is needed. MLPA uses probes to test whether the exon is there or not. Most likely your son has a deletion of exon 55 (i.e. exon 55 is not present). However, it is also possible that there is a small mutation within exon 55, which would mean that the probe cannot bind to exon 55. So a PCR test is needed to check whether exon 55 is deleted or not – generally this is done automatically, but please check with the team that did the diagnosis that this was done.
Several mutation specific therapies are available, such as eteplirsen (exon 51 skipping, would not work for an exon 55 deletion) and translarna (only for nonsense codons, not for deletions).
In India I know Dr Vishwanathan in Chennai – he has a lot of expertise with trreating DMD patients.

industry_corpus2: Health & Medicine


text: The seamless finish of these long compression running pants made from skin-friendly polyamide promises maximum freedom of movement and a perfect fit. The compression keeps fatigue at bay while you exercise and boosts faster regeneration afterwards. The reduced volume of material behind the knees keeps wrinkling to a minimum and enables you to run with confidence. An elasticated waistband with inner drawstring and an additional integrated key pocket enhance the functional aspects of these running pants.

industry_corpus2: Manufacturing


text:
Ocean Township’s Affordable Housing Trust Fund will get a real financial shot in the arm now that a 75-unit residential development in the western section of the township is starting to be built and occupied.
The developer has agreed to contribute $24,000 per unit to the fund, which will eventually be used if the township needs to develop more affordable housing under a state mandate.
Mayor Christopher Siciliano said that the first $72,000 contribution is based on six homes receiving their certificates of occupancy. The other $24,000 payments will be made as a permit is issued to build a new house, for an eventual total of $1.8 million.
The mayor said there is already $961,000 in the Affordable Housing Trust Fund.
The Shade Tree Commission will also get a financial boost, with the developer’s agreement requiring a $131,250 contribution. Out of the 80-acre site, about 20 acres were developed and the payment is primarily for removing trees from the site.
Siciliano said the site was originally proposed to have 498 apartments.
“Now there are only 75 single-family, age-restricted homes for seniors, that will have no impact on the school system,” he said.
Some residents had recently questioned the payments and if they were being made.
“So far (Toll Brothers) is 100 percent compliant and on time. There is nothing nefarious going on here. Everything is going as promised and as per the agreements,” Siciliano said.

industry_corpus2: Real Estate & Construction


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On this National #RoofOverYourHeadDay, we celebrate the joy of the Meus Family in Haiti who received a new roof over their head with the wonderful service of our very own Jennifer Olivera. HBC Group partners with Operation Starfish to help build homes in Despuzeau, Haiti.
On this National #RoofOverYourHeadDay, we are asked to give thanks and be grateful for all that we have!!!


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I can hear your voice in my head, even now, as I read the Henry V, especially the "Follow, follow" and "celerity." That IS a good monologue... maybe I should try to engage my rusty brain and memorise it. God, we all look so g-dd--mned young!! What show is the photo of you in the black veil from? I like it!
I don't have a favorite passage because I'm just not good at remembering that kind of stuff. But my favorite Shakespeare play was always Macbeth. It was so bloody and gruesome. The worst of all of his plays was Romeo and Juliet. Gag me with a royal silver spoon.
The first time I ever noticed Chris was when he was in Much Ado About Nothing.

industry_corpus2: Literature & Emotions


text:
AN ACT TO AMEND SECTION 99-35-115, MISSISSIPPI CODE OF 1972, TO REVISE THE PRESUMPTION AGAINST RELEASE ON BAIL AFTER CONVICTION OF A FELONY; AND FOR RELATED PURPOSES.
99-35-115. * * * A person convicted of a felony shall not be entitled to be released from imprisonment pending an appeal to the Supreme Court, unless it be so ordered by the court in which conviction is had, or by the Supreme Court, or by the judge who presided at the conviction, or the judge of the district in which conviction was had, or a judge of the Supreme Court in vacation of said court; and the making of such order shall be a matter of discretion with either the court or judge to be exercised with the greatest caution, and only when the peculiar circumstances of the case render it proper.

industry_corpus2: Law & Justice


text:
TEAMS took part in a series of games and challenges in the grounds of the Sue Ryder hospice in Nettlebed to raise money for the charity.
The It’s a Knockout-style event was organised by villagers Kate Russell and Jane Alexander Carr, of Ginger Goose Events.
Twenty teams of adults took part, including a team from interior design and home furnishing shop Life At Nettlebed, a group of residents called the Nettlebed Lads and some pupils from Shiplake College.
There were also 35 children involved.
Obstacles and challenges included “off to the shops”, a cargo net and inflatable slide which teams had to negotiate while carrying a bucket full of plastic food, and “the cry baby”, a relay in which participants had to crawl through an inflatable tunnel and throw a ball into a baby’s open mouth.
The winners of the morning session were A Class Team from Nine Mile Ride Primary School in Finchampstead and in the afternoon the Nettlebed Stingers netball team claimed victory.
Mrs Russell said: “We were absolutely delighted with the turnout. The weather was amazing, which really helped the whole ambience, and we had lots of spectators as people made a day of it. Thanks to everyone for their support — participants, visitors and sponsors.
“Because we both live in Nettlebed we are fully aware of the great work Sue Ryder does.


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The Allman Brothers Band drummer Jaimoe and The Revivalists guitarist Zack Feinberg and pedal steel guitarist Ed Williams will join The Marcus King Band in New Orleans during a Jazz Fest last-night show.
Watch The Marcus King Band perform three songs for Jam In The Van, including the brand new track “The Well” at South By Southwest.
The Marcus King Band will offer a free webcast of their Capitol Theatre headlining debut, which will begin tonight at 9:15 p.m ET.
Marcus King began playing the guitar when he was two years old; growing up surrounded by three generations of guitar players, now at the age of 16, it’s Marcus who will be leading his band to a steady rise. The Marcus King Band brings together Rock, Funk, Blues, and Jazz into a perfect melodic blend. Their influences span from the Allman Brothers Band and The Meters to Miles Davis and B.B. King. The MKB is a quartet of guitar, organ/keyboards, bass, and drums.


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A set of four cute shapes. Grab and go – wipe on your skin for a smooth quick and non-messy bit of moisture.
Moisture bars are lotion in a shape. They are fun and they work. These Nature Rich bars do the work of our normal lotion, but are more fun!


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According to surveys, around two thirds of tyres on UK roads are under inflated, sometimes by as much as 20%. Not only can this pose a serious danger whilst driving due to the risk of the tyres overheating, it also increases the carbon emissions generated each journey, while raising your car’s fuel costs. Ensuring you drive with correctly inflated tyres is one of the first steps to becoming a more economical and environmentally friendly driver.
Driving with under inflated tyres is a sure-fire way to lose fuel efficiency. With less air in the tyre, surface area with the road is increased, which generates more rolling resistance. This means that more fuel is needed for the car to achieve the same speeds on correctly inflated tyres, generating greater emissions. By not keeping your tyres at the correct pressure, it’s not just the environment that loses out, so does your wallet.
Ensuring your tyres are at the correct pressure is also important for prolonging their lifespan. Greater friction on the tyre increases heat generated, which can mean increased tyre wear or even a blowout. Tyres aren’t cheap to replace, so it pays to help make them last as long as possible. Correctly inflated tyres also help to reduce the risk of wear to other parts of the vehicle.
Tyre pressure is most commonly measured in pounds per square inch (PSI) or BAR pressure. Information on the correct tyre pressure can be found in your car’s manual, online, or sometimes printed on the driver’s door. Check tyre pressure using a reliable gauge while the tyres are cold. If the pressure is below the recommended level, it will need topping up. Most petrol stations offer free or very cheap air from machines which you can set to inflate to a certain pressure. It’s also becoming more common for stations to offer a service where someone will help you fill your tyres up using the machine.
Filling your tyres to the correct pressure can help to improve your milage by 3.3%, while keeping the carbon emissions generated by your journey lower. Just by remembering to check your tyre pressure every few weeks, you can save money, reduce your environmental impact and crucially, stay safe whilst on the road.

industry_corpus2: Automobiles


text:
With its Norwegian roots, it comes as no surprise that Telemark Inc. has an eye for world class design when it comes to building its distinctive homes all across the South Fork. Here, we meet Telemark’s Project Manager & Head of New Business Development Joe Sullivan, who tells us all about the company’s 40-year history, and how it is dominating the the growing market for sustainable homes.
Tell us how Telemark got its start, and how it came to specialize out east.
When Frank Dalene and his father came from Norway in 1954, his father started building in St. James and, throughout the years, moved further east. Frank established a carpentry contracting business after graduating college in 1976. His father’s Norwegian partner retired and in November 1978, Frank and his father merged their two businesses to form Telemark, named after the county in Norway of their roots.
A building recession up Island brought them to the South Fork, framing houses for high-end builders. Frank’s brother, Roy, a civil engineer working for Bechtel Power Corp, joined the family business, and in the early ’80s, they became a builder with a focus on producing the highest quality possible. That reputation led them to build some of the most remarkable buildings in the Hamptons, and the reputation continues today.
You offer a variety of building styles, from the traditional to the strikingly modern. How did you begin to master each of these?
With 2018 being our 40th year in business, we’ve been fortunate enough to work on all styles of building, from modern to colonial, farmhouse to contemporary, historic preservation and beyond. Our expertise in building all types of designs, materials, means, and methods with precision, quality, and roots in the carpentry trade makes us unique. We are well equipped to build to the design of the architect and needs of the homeowner (or business owner).
Do clients usually come in with a firm idea, or do you help direct them toward the home of their dreams?
It really varies from client to client. Some come with very detailed architectural drawings that we do not stray from and others have drawn sketches in the sand at the beach to show a general concept. Sometimes a project comes through an architect and sometimes we refer the architect, creating that team.
We enjoy working to give guidance and input to the engineer when necessary to ensure our clients are more than happy with their finished product.
Are there any builds you’ve had a hard time parting with, given the love and attention that went into it?
We are lucky enough to be able to hold onto many of our projects after the build with our Telemark Service & Maintenance division. We’ve kept some of our clients for over 30 years and continue to perform annual maintenance. Our clients are very happy and have peace of mind knowing that we are there during a hurricane or winter storm to look after their homes.
Since the high season in the Hamptons is the summer time, most of our completion deadlines are Memorial Day and Fourth of July, so that homes can be enjoyed during the summer months. Starting a project in the fall is usually the best time to get things going in order to have the summertime use.
Always remember, it takes sometimes a year or more to develop the design and receive all approvals for a building permit to start building.
Are there any “sleeper hit” locations that you think are the perfect spots for a new home?
It all depends on the demographic, but I really like the quiet areas around the water like Three Mile Harbor (both the Springs side and the Northwest side) or Amagansett. There are plenty of gems out there, you just have to be lucky enough to stumble upon them at the right time.
How did sustainability become a cornerstone of the Telemark brand?
Sustainability and green building have always been something that we have strived to incorporate into our building. Our first ads in 1978, naming the work we did, includes “Energy Saving Repairs.” It is a strong belief of ours that while continuing to be innovative, we encourage sustainable building practices in our building and to emphasize what we do best: creating an environment that is naturally pure, visually beautiful, and custom built to suit the needs of a distinguished clientele.
Founding the Hamptons Green Alliance, building the groundbreaking HGA House and now the Fossil Fuel Free at Frank’s house with unique, innovative means and methods has made Telemark one of the leading green builders in the country, with invitations to speak of around the world including The ZERO Emissions Conference in Oslo, Norway.
Tell us about LEED Certification. Is that something you strive for when building all of your homes, or is it requested by the client?
We incorporate many of the means and methods of LEED certified building, sustainability, and energy efficiency in our normal building practices today. Since all the homes we build are custom, the client determines if we will go through the certification process.
Among your other handyman services, you offer an Energy Audit. Can you explain that process and the results it can yield for the home owner?
Having an Energy Audit performed at your home is a very smart and important thing to do. Building science has really come around and many homes (even ones built within the last decade) have multiple points of energy loss and can be easily fixed by insulating around doors, windows, changing lights and fixtures, or installing smart home heating and cooling controls.
For most homeowners, an Energy Audit is free, allowing them to receive a report of deficiencies without the obligation to do the work if they choose not to. Or they can do it themselves. At least the homeowner will know where their energy is being lost and they can address it at their leisure.
To learn more about Telemark, visit www.telemarkinc.com or call 631-537-1600.


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Northern Ontario Rep Mark Harris has joined David Astley & Co.
You are here: Home / News / News / Northern Ontario Rep Mark Harris has joined David Astley & Co.
Mark comes to us with a background in law enforcement and sporting goods equipment sales. He has an impressive history with the Canadian Forces and has currently started his own business. We are excited to have Mark representing us in Northern Ontario!


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It's no fun getting sick on a vacation. If you do get sick while travelling abroad, it's important to use safe practices with medicines. The medicines you take at home may have completely different names in other countries. Even if you do find products with the same brand names as products you buy at home, they may actually contain different medicines or different strengths. SafeMedicationUse.ca has received reports showing the need for extra care when purchasing medicines in other countries.
One report came from a consumer who bought Reactine in Italy, thinking it was the same medicine she used at home for allergies. In Canada, the product called Reactine contains only cetirizine, a medicine used to treat symptoms of allergies. On closer examination, the consumer realized that the Italian Reactine product also contained pseudoephedrine, a medicine for treating nasal and sinus congestion. In Canada, this product would be labelled Reactine Complete Sinus+Allergy. Consumers who unknowingly take pseudoephedrine could experience unexpected side effects or drug interactions, putting themselves at risk of harm.
In another reported incident, a consumer was given the medicine Lemsip Max Cold and Flu while on a cruise. This medicine contains paracetamol (for pain and fever) 1000 mg and phenylephrine (for sinus congestion) 12.2 mg. This product is not available in Canada. The consumer was not aware that paracetamol is another name for the medicine acetaminophen, the active ingredient in Tylenol. The amount of acetaminophen in the Lemsip Max Cold and Flu product is much higher than what is typically found in similar products in North America. Consumers who don't know that paracetamol is another name for acetaminophen could unknowingly take too much of the medicine. An overdose of this medicine could cause serious damage to the liver or even death.
Whenever you travel, be sure to bring an adequate supply of all the prescription and over-the-counter medicines that you use regularly. Pack your medicines in your carry-on bag if you are travelling by plane. Bring enough medicine with you to last through a travel delay.
Be sure you know both the brand name and the generic name of all your medicines. Be aware that brand names as well as generic names may be different in other countries.
Always read the labels of medicines carefully, even if the names seem familiar. Check the active ingredients and check the correct dose to take.
Be aware that products with brand names similar to the names of drugs you use in Canada may contain more ingredients than the Canadian products - or even entirely different ingredients.
If you are uncertain whether a medicine you're given in a foreign country is the same as the medicine you're familiar with, ask a healthcare provider for advice. Healthcare providers in other countries may be able to find out whether the medicine is the same as what you're taking at home.
Keep your list of medicines and how you use them with you at all times. If you need to seek medical care while you are travelling, show the list of medicines to all healthcare providers. If changes to your medicines are made, ask the healthcare provider to help you update your list.
If you receive or purchase a medicine, review the details with a healthcare provider. For example, ask about the name of the medicine, the dose, what it is used for, and how often to take it. Let the healthcare provider know if any of the information you receive is different from what you expected.
Read more about avoiding problems with your medicines when travelling.
Read more about brand name confusion.
Read more about preventing harm from acetaminophen overdose.


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And that is where it sits. If we believe that Mr. Perp replied truthfully to Bragalia, and that Bragalia correctly reported it to us, then we have something that resembles a confession. Except that we don’t know who is making the supposed “confession,” or exactly what he is confessing to. So, Believe it or Not.
However, French skeptic Giles Fernandez pointed out that he had discovered several years earlier that this photo actually shows physics students from UC Davis visiting Intel, and suiting up in special ‘clean room’ suits, designed to prevent contamination of silicon wafers used in the manufacture of integrated circuits. It has nothing to do with Socorro or NMIMT. When this was pointed out to Bragalia, he blamed the error on his Webmaster, and said that the caption was being changed to “The Small Figures in White Coveralls, Similar to New Mexico Tech Physics Department in the Mid-1960s” (emphasis added). Why tech students in 1964 would be wearing suits similar to those used in contemporary Clean Rooms, designed to filter out the tiniest submicroscopic particles, was not explained. Or maybe he simply meant that the students had white overalls, like plumbers and handymen sometimes wear. How incredible would that be?
Dr. Frank Etscorn, New Mexico Tech administrator and behavioral psychologist, reportedly affirms the event to be a hoax. One of his graduate students reportedly investigated and solved the “mystery” of what happened, and who was involved. Unfortunately, further details are not available.
“We come back to the speeding car, which started the whole business. We certainly would like to know more about this. You have made it clear that Zamora was a gruff type, who enjoyed giving out tickets. It seems entirely reasonable that he might have antagonized some of the local teenagers, who devised a hoax to get even. This explanation, I might add, independently occurred to both Lyle and myself. The whole thing could easily have been planned to come off about as it did. The car came into his line of sight from a side road. Which side road? Could it have been from the direction of the flame and roar? Apparently Zamora thought he knew the occupant of the speeding car (Vivian Reynolds?) Was this driver ever found and questioned as to what he heard or saw? Did Zamora have a regular patrol route so that his approximate whereabouts would be known at a given time?
In other words, we see as the most likely possibility that someone planned the whole business to “get” Zamora.”(p. 142 in case documents scanned by Paul Dean).
As the investigators were leaving the actual site, they noticed an area approximately 1 3/4 miles away, which gleamed in the sunlight. Extracting binoculars from their vehicle, they viewed what appeared to be an abandoned aircraft junkyard. Later, they discovered that the aircraft were part of the property of a local technical school – New Mexico Institute of Mining and Technology. This information was obtained from a clerk who works for the City Court system. He warned the researchers not to enter the storage area, because two men were recently convicted of breaking into this property. GSW’s team became curious and decided a closer look at the area was warranted. They traveled on a road through the technical school’s campus and came upon a barrier.
Walking some distance away from the road they found a point at which the contents of the storage area could be viewed. To their amazement, the area contained a large variety of both segmented and intact aircraft. There appeared to be some Navy and Marine jet fighters, some Bell “X” aircraft and a nose section of a large ballistic missile.
GSW determined that the property did indeed belong to NMIMT. They contacted C. B. Moore, professor of atmospherics, and a man who plays a significant role in UFO history quite independent of this, primarily because of his connection with Project Mogul. Moore told them that the junked aircraft were part of the Terminal Effects Program, which began in 1947, with most of the aircraft arriving during the 1950s. Moore replied to GSW that he had investigated the Zamora incident on his own, “and can assure you that there is little probability that it had anything to do with students or the Institute. If we can believe Officer Zamora (and there is no reason except for the strangeness of the observation that we should not), then it appears that he saw a Lunar Landing Module (LEM) but his observation was at least 12 months before the module was first tested here.” A very strange comment, indeed!
How did the two students in white overalls make themselves disappear, especially since Zamora and Officer Chavez were walking the site of the alleged landing just a few minutes later? This would seem to require something like a magician’s disappearing act.
Bragalia’s supposed “Perp” is allegedly a professional man unwilling to open himself up to humiliation and scorn, and professional damage, over his role in this incident. However, Blogger Curt Collins recently wrote about two men, a Professor of Radiobiology and a Senior Biologist, who confessed in 1976 to perpetrating a ‘still unsolved’ UFO hoax at Oak Ridge National Laboratory about 1951. As far as is known, neither of the two men suffered any repercussions from this.
Dave Thomas, founder of the skeptical organization New Mexicans for Science and Reason, is a NMIMT graduate. To look into the possibility of a hoax originating with NMIMT students, he set up an internal website available only to those who are students, employees, or alumni of NMIMT. Its purpose was to allow people to tell what, if anything, they knew about the 1964 Zamora incident. While a few people expressed the opinion that it was a student hoax, there was no specific or useful information obtained from anyone. This strongly suggests that no ‘student hoax’ existed.
Thomas has suggested an interesting possibility of what Zamora may have seen. According to documents obtained from the White Sands Missile Range, “on April 24, 1964, there were special tests being conducted at the north end of the White Sands Missile Range (WSMR) involving a helicopter used to carry a Lunar Surveyor around for some tests… Surveyor was a three-legged, unmanned probe, which was used to learn about the moon before the Apollo program got there….The Surveyor tests were done with a small Bell helicopter that supported the craft from its side… The tests missions were manned by a helicopter pilot and a Hughes engineer – two persons, in white coveralls.” Not only does the time of day of this planned test (morning) not match Zamora’s sighting (which occurred just before 6 PM), but this is a long way from Socorro, about 80 miles as the helicopter flies. Still, as Thomas notes, “things don’t always go “according to plan,” and many tests which have defied completion by morning have been known to somehow get finished up in the afternoon.” The possibility of the Surveyor testing cannot be ruled out.
In 1996, engineer Eugene Robinson of Indiana University suggested that what Zamora saw was an early version of a propane-powered hot air balloon. This explanation has been largely ignored by UFOlogists. It was not even mentioned by Randle in his Socorro book. When asked why, he replied that it was a “non-starter.” I’m not so sure about that.
The propane burners on such a balloon make a loud “woosh,” as Zamora described hearing. It seems quite likely he may have seen an experimental two-man propane hot air balloon briefly land, then take off again. In fact, that suggestion seems to best match the details Zamora reported. Might this two-man balloon be what Zamora saw?
Given all these conflicting yet plausible explanations, it is difficult to say for sure what Zamora saw. Unless someone can explain convincingly exactly how the supposed “student hoax” was carried out, I will assume that the unexpected landing of a newfangled propane hot-air balloon is the most likely explanation for this classic UFO incident.

industry_corpus2: Subject Education


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All students must have a medical release form on file, otherwise they will not be permitted to participate in class. New students- please complete/return the annual registration paper work and $45 fee within one month of first class.
The studio will close April 15th - April 19th for Spring Break (these dates are not reflected in the 20 week session, therefore tuition is not pro-rated nor are make ups necessary).
The studio will be closed on Memorial Day (these classes can be made up at your convenience).
Please place payment in drop box, checks do not need to be placed in an envelope however please write your child‘s name in the memo section. Cash must be placed in an envelope with child‘s name on the front. $10.00 late fee will be charged for tuition received after the 10th.
Recreational classes will be cancelled when Orrville City Schools close due to inclement weather. Make up classes will be available.
We do NOT offer a babysitting service therefore we are NOT responsible for those left unattended.
Parents please watch your child’s class from the designated area. Competitive practices are CLOSED for viewing.
Thank you for allowing us to coach your children, we sincerely appreciate the opportunity!
Copyright @ 2007~Heather's Studio, Inc.


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By default the invoices will show the address, Attn, etc., on the client level but this can be changed per Project. Follow the steps below.
The invoices for this project will adjust automatically and will not affect any other projects under this client. Do this for any project that is separate from the client settings you already setup in the program.


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The Arcadia Three Light Bath Sconce by Troy Lighting establishes a classic, traditional element to any interior along with soft, elegance illumination. The Arcadia Three Light Bath Sconce is composed of a glass body with metal attachments. The Arcadia Three Light Bath Sconce combines timeless beauty with modern, high tech materials.
Height: 8.75" x Width: 22"


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"Under this SNP Government, GP services are under funded and under pressure.
"In surgeries across the country the recruitment crisis is causing staff to consider their own futures, yet just a handful of recruits have been secured through this flagship scheme.
"Between flatlining recruitment schemes and a Conservative Brexit disaster that is pushing vital medical staff away from the UK, the pressure on the hardworking staff who remain is intolerable and unsustainable.
"It is time the Scottish Conservatives joined the case for an "NHS passport" for EU health staff and the SNP put a mental health practitioner in every surgery, taking some of the pressure off GPs and ending the scandal of poor access to mental health treatments."


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American Airlines has a new ‘Last-minute Holiday Bonus’ that can earn you some easy miles when you shop through their shopping portal.
During the “Last Minute Holiday Bonus” bonus campaign, which runs from 12/01/17 through 12/17/17 at 11:59:59 pm ET (the “Bonus Period”), Member will earn a one-time bonus of up to 1,500 AAdvantage® miles on qualifying purchases, in addition to the standard AAdvantage® miles earned from shopping online through the AAdvantage eShoppingSM mall.
Spend $150, earn 500 bonus miles.
Spend $300, earn 1,500 bonus miles.
This bonus adds 3.3X-5X AA miles in addition to the normal payout you will receive from the portal. It’s a good idea to still use a comparison site like Cashback Monitor to make sure you are getting the best return. But, usually these bonus will give you great rates. Happy shopping.


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Opening a retail store takes many hours of work and we want to you to be protected for your investment. Claudia's Insurance Incorporated offers many different options to protect your retail store operation in Florida.
Many retail stores have the same basic insurance needs whether your selling books, crafts or jewelry. We can evaluate your risk for damage and liability for your retail stores in and around Cutler Bay. Retail stores need insurance to protect themselves from damage that may occur to their inventory or accidents to your customers.
Contact us to find out more about retail store insurance in Cutler Bay, Florida including the Coral Gables, Cutler Bay, Homestead, Miami , and Pinecrest areas.

industry_corpus2: Finance & Economics


text: A millennial classic from Erykah Badu – a record that came along right as the current century was starting up, to show a soulful path that would keep things strong for many years to come! The album grabbed a bigger audience than Erykah's first, but still kept things strong – really focusing in on that amazing vocal style that made the singer such a unique talent – and which always had edges that were sharper, and runs that were deeper, than some of her contemporaries who might be able to trick a phrase with a bit of spirit, but never deliver the whole thing in the way that Badu can! Themes are both personal and hinting at her political turns to come – and titles include "Kiss Me On My Neck", "Didn't Cha Know", "My Life", "AD 2000", "Bag Lady", "In Love With You", and "Booty". © 1996-2019, Dusty Groove, Inc.


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New to 3D Printing, Please help!
I have done all the calibration of the stepper motors and entered the correction in to the Firm ware. this seems like under extrusion. How do I fix this? This was the 5mm calibration cube.
That Orange color is wicked! So is your printed part. Evil maybe. I don't think there is very many of us that hasn't made a part just like that. Watch this video from YouTube and Tune your stepper motors.
https://youtu.be/XU6lgFeZ7ZQ Then try your print again. Crank your feed rate as slow as it will go and watch to see if your part is adhering to the table. Sometimes, I will run my part slow to get good adhesion then crank it up to 100%.
You can also adjust adhesion by changing the setting on the Slicer Adhesion Type: "none" "Brim" or "Raft".
Be Patient. Read lots of Posts. Experiment a lot. You are on the road to making a lot of really cool stuff.
It will be a week or more before I can get back to see how you are doing. But please let us know how you are doing and what worked for you.
I will be surprised if there are less than 100 more post replies with ideas to help you.
Looks like you dug into the build plate.
When you start the print, watch the first layers, if you see it's peeling up right away, or just dragging around, bring the Z axis higher, if it looks like its really mashing the plastic down or if all you hear is "thump thump thump" that is the extruder skipping and you need to bring the z-axis lower.
If the first layer doesn't look right, stop the print and try again.
Double check your bed level using paper WHEN THE BED IS AT 60C OR MORE- if you usually print ABS, check level at 100C if it's PLA 60C if it's PETG 70C.
Thanks but nIhave tuned the stepper drivers already. twice a least.
If your voltage is indeed set correctly and you are between 105 and 110 steps per mm you should be fine.
Next is to check bed level/Z axis offset and make sure temps are correct.
Really bad filament can cause jams at worst, but usually will just cause minor print defects such as under and over extrusion or stringing.
What do you maen when you say "as long as you 105-110 steps per mm" Where do i caeck this?
I am used Hatchbox 1.75 PLA. Thanks for all your help.
I did use paper at 60 deg C this time . Good advice I forgot about thermal growth. I have gouged the print surface a few times. I will buy a new one once i get this figured out.
Thank you for your advice. I have tune evrerything x,y,z and extruder. This must be a settings issue.
Someone on FB wanted to see the first layer.
Too high, if you see gaps in-between the lines you are most likely too far off the bed.
What do you have as initial layer height in your slicer?
Also, try printing a wide flat surface like a 40x1 plate.This will allow you to get a better idea what is happening.


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Much Less is Much More.
ONE ZERO is a fusion of advanced product design and condom technology. ZERO condoms are 25% thinner than ONE's standard condoms, so you can feel closer to your partner than ever before. ONE has also added some extra room at the base and tip for maximum comfort, and a secure fit in the middle so you can push your sexual limits with confidence. This condom is so advanced, you'll barely know its there! When choosing ONE you’re helping people in need. A portion of every purchase supports HIV/AIDS prevention and treatment efforts in Africa.
SIZING TIP: if you require a more tailored fit, but desire advanced ULTRATHIN technology, try Beyond Seven condoms.
PERFORMANCE TIP: ULTRATHIN condoms require additional lubricant to enhance pleasure and safety (reduce breaking).
Just bloody brilliant condoms. I'm a big fan of One, and these and the 'Senstive' kind are a must buy. Feel amazing. So much better than other big brands. And a circular packet, which is novel!
Love "One" brand in general and these are very thin and comfortable. I wear medium and these fit well.
I am so glad I stumbled upon thecondomreview, because it's definitely changed my (& especially my boyfriend's!) condom experience. ONE ZERO is in my top 3 list, & for good reason...it's thin enough to let you feel like nothing is there, but strong enough to make you feel safe, & overall just feels wonderful. I'm kinda iffy on ONE condoms in general (only because we found a few that just didn't work for us), but this one is certainly worth investing in. We love it!
This is a very good condom, and with a sexier name and packaging than the Durex Extra Sensitive, with which it otherwise is pretty comparable. The Durex is slightly bigger at the base and head - they're both pretty standard midshaft - and maybe very slightly more sensitive. But there's not much difference, so you may prefer this.
My love of One condoms expands every time I try another one of their products. The One Zero is my favorite, and I've tried many of them! Feels really like nothing and so smooth and silky. My one complaint is that I was a little disappointed in the wrapper. I'd love to see these condoms in one of their unique wrappers. While this condom is worth buying and using on it's own merits, it's also a less expensive alternative to the ultra thin Japanese brands. As with any ultra thin condom make sure you add lube.
The One Zero condom is going to give Japanese condoms a run for their money. Totally sensitive. We used extra lube as instructed by Lucky Bloke and it made the experience so slick. God, we love this condom review!!
We have found so many truly superior condoms during this review. Each one seems to get better! The Zero condom is no exception. So thin and super comfortable. Wow!

industry_corpus2: Biopharmaceuticals


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A St George’s cricket player pushed the Minister of National Security in a scuffle at Cup Match, a witness has said.
He was speaking after a man at the match told The Royal Gazette he saw player Treadwell Gibbons push Mr Caines.
He added that the tension was quickly defused and ended after a few seconds and the two men hugged.
The witness said Mr Caines was among a small group of Somerset supporters who had entered the field during the game to celebrate significant moments.
He said: “It was on Friday afternoon, towards the end of Cup Match. Somerset had gotten one of the last St George’s guys out.
The witness said Mr Gibbons pushed Mr Caines and the two exchanged words.
He said they hugged before going their separate ways.
Another witness confirmed that there appeared to be an incident that involved the two men, but that he did not see any physical contact.
He said: “I didn’t see anything physical and it was all over in about a minute.
A spokeswoman for the Bermuda Police Service said no incident had been reported.

industry_corpus2: Sports


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Just the other day, I shared a list of 6 Inspirational Books from Breast Cancer Survivors. Today, I wanted to share a handful of books that are written for kids who have parents with Cancer. A majority of these are written with Breast Cancer as the main focal point but there are a couple that could be used in any Cancer situation.
I hope that you never need any of these but I believe it's always good to have somewhere to look for resources. Especially when it comes to speaking to our children about tough subjects such as Breast Cancer, etc.
Maya Silver was only 15 when her mom was diagnosed with Breast Cancer. This inspired her & her father to put together a book to address the subject of Cancer focused towards teens. They took their personal story, added advice from Medical Professionals & other teens' personal stories. In the end, they created a wonderful book full of guidance & testimony. A book to let teens know that what they are feeling is okay & that they are not alone.
In this heroic tale, Jonny is a Superhero whose mom is sick. Not knowing what to do, he takes a trip to the hospital along with his friend Bear. They watch the hospital workers & learn what they do. Teachers & Doctors will also find this book highly resourceful for multiple reasons. It teaches patients about the hospital, can be applied to any family member (not just mom), & it covers a number of different themes.
This book shares fun & practical ways that children can become involved in the recovery process when someone in their family has Cancer. There are two different ways that this book can be read. It can either be a simple read for the younger kids or a more in-depth read for the older ones. The author found out, through her own personal battle with Breast Cancer, that her kids were important in helping her get better.
This book helps with talking to your young child about Breast Cancer. It addresses what will be happening in the upcoming weeks & months with their mom's recovery.
Author Sharon Amerson is also a Breast Cancer Survivor. This story addresses the difficult task of sharing a tough subject with a child. But it also shows how love, compassion, & family support can help make tough times easier. And sometimes the biggest inspiration comes from the smallest members of the family.


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Saga Dawa festival is festival falls on the forth month of Tibetan lunar calendar. This festival is celebrate to commemorate the Birth, enlightenment and the parinirvana of the Gautama Buddha, the principle teacher of the Buddhist. It is believe that the lord Buddha was born, attain enlightenment and achieve Parinivana on the same day, which is on the 15th of the forth month of Tibetan lunar calender.
This month has been purely a religious month in every Tibetan society. There are lots of religious custom develop as per the local traditions and believe. i am writing here some of the most common traditions.
It is must to visit temples and monastery and make offering to the three jewels of Buddhism. The three jewels of buddhism are Buddha (the teacher), Darma (his teachings) and Sangha (the religious community). although it is universally hold Sangha as a monks community but there are some who believe that Sangha is a religious community of who ever indulge in religious practice, not necessarily the monk communities. It is commonly encourage people in abstaining indulging in practicing evil deeds, it is believe that if an individual practice evil deeds the sin accumilate would be thousand times and if some one does a positive deeds, he would accumulate thousand fold positive virtue or karma.
In Lhasa people would go to visit Jokhang temple and some other religious center around Lhasa. There would to different monastery and religious place for pilgrimage. Every single individual has a group religious freinds and there would contribute the money for group religious practice. One of the most popular religious group activity is to make offering to the entire statue in Jhokang temple, and go to visit some monastery in distance and make offering there.
In Darchen near Mt Kailash. Local people and devotees who visit the mountain for the pilgrimage would participate in change the religious flag. This traditions of changing the darchen falls back to historical dates. Darchen literary means the big flag.
One of the most common practice during the month is to abstain consuming meet and adopting vegetarian diet for the month. The fifteenth day of the month, it is believe to be the exact date for Buddha birth, nirvana and parinivana. During the day people would indulge in religious activities. this is like the D day for Tibetan religious activities. If you visit Tibet during the day, you will be able to witness religious activities of Tibetan community.


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Ah, childhood. Those fond memories of yesteryear from before a time of paying bills, having a job, and getting away with not bathing regularly. We could just plant ourselves on the couch and watch some of our favorite cartoons without a care in the world. We may be forced to get older, but growing up is optional. We want to keep those Nicktoons with us, and not just in our hearts. They can actually help us be productive as well, which is a far cry from what they did long ago.
Celebrate some of the 90's most classic cartoons with a Nickelodeon-themed notepad. Sectioned off by Nicktoon character dividers, this pad has college ruled lined pages and graph paper. Perfect for whatever work you may be in the middle of... also for doodling.
College ruled lined sections for writing and graphing sections for math. Both sections make excellent doodle pads as well. We know because we tested to make sure.
Dimensions: 8 1/2" x 6 1/2"


text: Sierra Vista Glass can save you money with costly windshield repair. Check out the leading auto glass firms in AZ. Save time by getting a repair directly in continental, AZ. You can trust Windshield Guru. We have the service providers you need.