MORE than 400 local councils and six state and territory governments will now have access to new guidelines to better assess and apply conditions to permits for heavy vehicles.
National Heavy Vehicle Regulator (NHVR) chief executive officer Sal Petroccitto said the release of two guidance documents would deliver consistency and standardise the conditions that can be applied to a heavy vehicle permit.
"The Road Manager's Best Practice Guideline for Applying Conditions provides invaluable direction to road managers on the types of conditions to be applied in a permit.
"Whereas, the Standard Conditions – Legislative Requirements outlines the key operational requirements for class 1 heavy vehicles carrying, or designed to carry, a large indivisible article and special purpose vehicles. This will assist operators to better understand their legal requirements and provide increased confidence in the process.
The NHVR has developed and implemented the documents as a result of extensive consultation with local and state government road managers to ensure they were fit for purpose.
They aim to assist through providing a step by step guide to assessing application and applying conditions, consideration when applying conditions, example sets of standard road and travel conditions, and examples of conditions covered by the law.
Importantly, they also call out invalid conditions and the reasons why they are not required on a permit.
Australian Local Government Association president Troy Pickard said accurate and reliable permit conditions were a big win for road managers working in councils across the country.


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Episode 104: MS Fatigue with Dr. Ekaterina Dobryakova
Fatigue isn't only a common symptom of MS; it's also one of the most disruptive symptoms of MS. It's hard to be out living life when you're trying to overcome that feeling of just not having any gas left in the tank. My guest is Dr. Ekaterina Dobryakova, a research scientist at the Kessler Foundation's Center for Traumatic Brain Injury Research, where she conducts research in cognitive dysfunction caused by traumatic brain injury and multiple sclerosis. Dr. Dobryakova's research has shown that there may be a behavioral intervention — a treatment that doesn't involve any drugs — that can effectively reduce MS fatigue.
We're also talking about the letter that former NBA championship-winning head coach David Blatt wrote, announcing his primary progressive MS diagnosis. We'll tell you about a discovery at UCLA that may explain why women are three times more likely than men to develop MS. And we'll tell you how you can join more than 4,600 people living with MS and be a part of an epic MS study from the comfort of your own home.
Coach David Blatt's Letter About His Primary Progressive MS Diagnosis 1:15
X-Chromosome Gene May Explain Why Women Are Diagnosed With MS 3 Times More Often Than Men 8:29
Your Opportunity to Participate in the Slifka Study 11:54
My Interview with Dr. Ekaterina Dobryakova 14:15
Subscribe to RealTalk MS or Just Ask Alexa 29:14
STUDY: The X-Linked Histone Demethylase Kdm6a in CD4+ T Lymphocytes Modulates Autoimmunity
Participate in the Slifka Study
Guest: Dr. Ekaterina Dobryakova
Tags: MS, MultipleSclerosis, MSResearch, MSSociety, KesslerFdn, Coach_Blatt, UCLA, RealTalkMS

redpajama_set_name: RedPajamaCommonCrawl


The 6" Cook's Knife from Wusthof's Classic Ikon Series is a workhorse in the kitchen. Also called a Chef's Knife, this tool will slice, dice, chop, mince, and more ! The knife is perfectly balanced, so your hand won't become fatigued when using it. This knife is made for those who prefer a smaller cook's knife. It is used for coarse or fine chopping, mincing, and dicing of virtually anything.


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European Yacht Charters uses a system with live links to our partners. This allows you to access the best discounts as soon as they are offered.
There are always great charter deals available. Save time and money by letting us help you chose and book your perfect charter boat.
If you currently own a boat, you can join our charter fleet. To find out how to get involved, please follow the link to Contact Us.
European Yacht Charters is a Spanish SL company based in Port Ginesta, Barcelona. Our background is in yacht sales and brokerage. We have almost thirty years' experience in the marine industry in the UK and throughout Europe.
European Yacht Charters is partnered with a worldwide network of over one hundred Charter and Broker companies. This partnership enables us to offer a comprehensive range of yacht charter options to suit your holiday needs.
On our site you can see our extensive portfolio of boats and yachts in Europe and Worldwide, at great low prices. We offer a diverse range of yachts for charter, including popular brands such as Beneteau, Jeanneau, Bavaria, and Dufour.
We are also in the process of building a dedicated charter fleet, right here in Barcelona. If you're looking to buy a boat for charter and want to get started, please get in touch.
From our office in the heart of Port Ginesta, European Yacht Charters can effectively market your yacht for charter. To find out how to join our charter fleet with a new or used yacht, just send us an email or call us. We are ready to help and answer your questions.
For hundreds of people each year, a Yacht Charter is the most exciting way to get into sailing. Perhaps now is the right time for you to begin this fun and fascinating hobby? You might want to get started as a solo sailor or with family and friends. First of all, planning your charter holiday should be part of the fun and the beginning of your adventure.
Our advice is not to feel pressured into booking a holiday quickly just because it's cheap. Everyone wants a great deal but make sure you research local weather conditions and sailing area when choosing your charter location. There are hundreds of charter companies to choose from and thousands of yachts available from reputable companies. Our advice below is intended to help a novice, planning to take an enthusiastic family on a one-week sailing holiday, for the first time.
Don't go anywhere that you are going to get too much wind. Attention to weather conditions is especially important if you are taking a less enthusiastic and/or nervous family along on a charter. The primary objective of any family sailing adventure is to make sure that everyone has a great time and wants to go sailing again.
Most charter companies will not allow you to take a yacht out without a Skipper's License. In addition, unless you have had some years of sailing experience, it's not advisable to charter a yacht in unfamiliar waters on your own. There is no shame in having a paid crew member to help – allowing you to relax and enjoy your holiday.
Unless you decide to leave everything to a Skipper, it might be an idea to let the charter company know where you intend to sail during your holiday. A professional skipper will keep an eye everything on the yacht – including morale and comfort of all on board. He/she might suggest that your crew need a little shore time to keep spirits up. Lots of decisions will be made during your charter. Don't be afraid to express your wishes to your skipper. They will have lots of local knowledge to share with you and ideas of where to sail. Just remember, if you end your holiday with a happy family who want to sail more, then you have succeeded.
Once upon a time, many yachts were narrow and uncomfortable down below. The possibility of a hot shower usually only came at the end of a trip, when you finally got home! Modern yachts have all mod cons and comfort, and often marinas offer very convenient port facilities. If you want your family to really enjoy their holiday, charter the biggest boat you can afford. Look for bedrooms which are comfortable and spacious for all on board. As a general rule, try to make sure that everyone can have some private space. Converting a bed in a saloon is never a great idea for a whole week and may detract from everyone's holiday experience. Look for enough cabins to provide berths for all – remembering a Skipper will require a cabin alone.
If your budget stretches to it, let the charter company provision your yacht. Many will ask you for a likes list and provide a decent amount of food, on board ready for you. Remember you are probably travelling to a strange country and you only have a few days holiday. So, do you want to spend your time shopping for food on the first day? If so, check where the shops are and think about carrying all the provisions back to your boat without a car!
Talk to us at European Yacht Charters about your holiday plans as we can offer helpful tips and advice. For example, we suggest bringing your kit in soft bags as they tend to be more yacht friendly. Soft bags are easier to stow, giving you more room on board. Suitcases can cause damage and wheel marks to your charter yacht and so don't make you popular with charter companies.
Your chosen cruising area should depend almost entirely on your level of experience. For example, one might think that Greece is a safe bet, which it often can be. However, even Greece – like all hot countries – has extreme wind conditions to deal with at various times of the year. Before you book, take a look at past local weather patterns for the time of year for your charter area. Also ask the charter company directly for advice regarding the weather during the month you plan to book your holiday.


Homemade lathe cathead intended to support a bar for turning when utilization of a steady rest is not feasible due to a lack of true round surfaces on the workpiece.
Be the first to comment on this DIY Lathe Cathead, or add details on how to make a Lathe Cathead! Click the "add comment" button above to comment.


From the 605 Freeway exit Whittier Blvd East. Drive about 1.25 miles East and turn Left on Philadelphia Street. Whittier High School is on the left side of the street. The entrance is on Whittier Avenue at the Library - "D" Bldg.
For driving directions to WHS using Mapquest - Click here, enter the starting address and click the "Get Directions" button under the "Ending Address".
For an area map view of WHS using Mapquest - Click here.


MC Gui is one of the most famous singers in Brazil, his music and lyrics transmit something new to the country's funk scene. His flavor conquers every moment, with notes of flavors that he developed, a flavor designed for all his fans. An irresistible mint-bubble gum flavor.


Whereas, government must not use laws or the color of law, regulations, zoning ordinances or the dictates of permits to violate, trespass on or restrict the rights of farmers simply based on the fact that they engage in farm-related commerce, and farmers are entitled to fair, reasonable and full remedies from government agencies or political subdivisions that violate or trespass on their rights.
Be it further resolved, that this resolution be published and disseminated to the Chairman and members of the State Central Committee, and to the Republican members of the Virginia General Assembly, and that it be posted to the RPV website in a publicly accessible area.
Update – Your Calls are Helping Property Rights!


I Have Arrived at the Hilton Nairobi this Morning for 4th African Regional Summit.
Kivumbi at Hilton Nairobi for African Regional Summit.
The Nairobi Convention organized by the African Telecommunications Union (ATU) powered by the Government of Kenya which has begun today 20th– will end on 25th July 2015. Am privileged to represent Heal The Planet Global Organisation-HTP seated in our beautifully organized table with a plastic card of our organization. I'll be bringing you the latest updates on this convention.
Meanwhile security is beefed up here in Nairobi where the President of the most powerful and richest nation on earth Hussein Barack Obama of United States of America is due to arrive this weekend. The FBI and multiple security agencies are rooting around.
I have earlier gotten dreams meeting Obama and his counterpart Uhuru Kenya of Kenya and I hope I will be given opportunity to share with them about my United States of Africa Dream which in 2012 I spoke about when I held a Public Lecture at the University of Nairobi, University of Dodoma & University of Dar-e-salaam. At that time I also visited Arusha, Moshi, Bukoba, Mwanza & Eldoret.
I held diplomatic and political talks for peace with militias who were fighting in Eastern Democratic Republic of Congo which transpired into putting down weapons and a peace deal.
This time round in this convention I will expound on Africa 54 an HTP Agenda and the United States of Africa Dream as well as lobby for support from more than 200 delegates from all African Nations and most powerful companies of the world like Facebook, ESO, ALION, EUTELSAT, HUAWEI, GSMA, Multi Choice, Boeing, FCC, Inmarsat, Intel, Safaricom, YASMI, GEW, IARI, Airtel Kenya, GSM, BR, Access, ABS Satellite Partnership and many others who are attending this convention.
The 5 day East African Telecommunications Commission (EACO) Congress which I attended recently with Princess Scovia Kivumbi at Sheraton Hotel Kampala opened major doors for me like this one has done.


Participants need to take care of their own accommodation.
Forty rooms have been pre-booked at preferential rates at the Ibis Styles Hotel (conference venue). If you would like to stay there, use the booking form available here. We invite you to fill it in and email it to Mr. Marc BRASSART as soon as possible because rooms will be attributed on a first-come, first-served basis. Please note that preferential rates are valid until 11 August 2018.
If you would like to stay at the Martin's Agora Hotel and benefit from preferential rates, fill in this booking form and email it to Samuel. Please note that preferential rates are valid until 11 August 2018. Situated right in the centre of Louvain-la-Neuve, Martin's Agora Hotel is a 10-minute walk from the conference venue. A map of the route can be found here.
If you are looking for other types of accommodation in Louvain-la-Neuve, you can check the AirBnB site, which offers a wide range of rooms and flats, or use the attached list of B&Bs on campus.
Since Louvain-la-Neuve is a largely pedestrian town, there are no permanent taxicab stands. All of its cafés, restaurants, and shops are within walking distance, though, so everything can be done by foot. Here is a map of Louvain-la-Neuve.
Wavre is a city located in the vicinity of Louvain-la-Neuve.
If you want to book a room at the Ibis Hotel in Wavre, use this link and you will automatically get the UCL promotional rates (UCL codes are pre-filled on the booking form). The hotel has a free car park and is close to the centre of Wavre (shops, restaurants).
Take exit number 8A on the E411 motorway (Brussels-Luxembourg). See route here.
(14-minute journey) There are several bus stops in Wavre where you can take a bus to Louvain-la-Neuve (TEC bus line 20). The timetable is available here and here.
Walk to the train station (13-minute walk; see possible routes here) and take the S20 train.
Since there are no direct trains from Wavre to Louvain-la-Neuve, you will need to make a connection in Ottignies. Once you arrive in Ottignies, you have two options: take the S8 train or a taxi to Louvain-la-Neuve.
Do not confuse Louvain-la-Neuve with Louvain / Leuven, situated in the Dutch-speaking part of Belgium.
It is possible to check train timetables and purchase train tickets through the Belgian Railways (SNCB) website and the SNCB app.
If you decide to take the train to Louvain-la-Neuve, you will then need to walk from Louvain-la-Neuve train station to the conference venue (14-minute walk; see route here).


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Money Matters: Investing in ESG
Find out what ESG investing is all about and how you can invest in ESG with MONEY FM 89.3 Presenter Rachel Kelly and our guests in this series of Money Matters.
Sessions are suitable for those with basic or no background knowledge of ESG investing.
30 June, Wednesday, 12PM-1PM
Part 1: ESG and Sustainability Investing 101
What exactly does ESG means and why it matters? Find out how 'going green' or investing in sustainability linked products, portfolios and companies can grow your investments. Join Prime Time Presenter Rachel Kelly and Samuel Rhee, Chairman & Chief Investment Officer of Endowus for this session as they discuss some key terms such as 'sustainability reporting', 'greenwashing', and help you enhance your knowledge of this burgeoning sector.
Samuel Rhee
Chairman & Chief Investment Officer, Endowus
As the Endowus Chief Investment Officer, Sam heads the Investment Committee and ensures holistic portfolios for every investor, including the Endowus ESG Portfolios. He is the former CEO and CIO of Morgan Stanley Investment Management in Asia and has 27 years of institutional investing experience in Singapore, Hong Kong and London. Endowus solves the biggest problems of wealth and investing, including retirement adequacy, which has led to the firm becoming the first & only digital advisor for CPF investing in Singapore.
Watch the live webinars and stand to win a Hydroponic Mini Garden, worth $68 each!
7 July, Wednesday, 11AM-12PM
Part 2: Ready To Grow Your Green By Going Green? How To Invest In ESG.
Interested in ESG investing but not sure how to go about it?
Join Prime Time Presenter Rachel Kelly and her panel of guests for this session as they look at different products and trends - from investing through your CPF to understanding ESG indices. They will be taking a close look at the components of different ESG funds, help you to understand the breakdown, and walk you through wider industry trends to help you make informed decisions.
Sherene Ban
CEO, Singapore & SEA, J.P. Morgan Asset Management
Sherene Ban, Managing Director, is Chief Executive Officer for Singapore and South East Asia for J.P. Morgan Asset Management. In this role, she is responsible for overseeing all aspects of the firm's asset management business in the region.
Sherene is a trustee director of the JPMorgan U.K. Retirement Plan and she sits on the Investment Committee. In addition, Sherene is on the board of JPMorgan Asset Management (Europe) S.à r.l. and is on the Executive Committee of the Investment Management Association of Singapore (IMAS).
Sherene obtained a B.Sc in Bioengineering from the University of California, Berkeley and an M.Sc in Financial Engineering from Princeton University. She is a CFA Charterholder.
Lily Choh
Singapore CEO & Head of Institutional for Asia Pacific, Schroders
Lily Choh is Singapore CEO and Head of Institutional for Asia Pacific at Schroders. She joined Schroders as Head of Institutional Business in 2008, to lead business development for the Schroders' Southeast Asian institutional business. She was appointed as Head of Distribution for Southeast Asia in 2017, whereby she was responsible for the management of the institutional and intermediary business, strategic partnership and activities across Southeast Asia. She was appointed Head of Institutional for Asia Pacific in 2019 and Singapore Deputy CEO in 2020.
Lily holds a Bachelor of Science in Chemistry from the National University of Singapore. She is also a Chartered Financial Analyst.
MONEY FM 89.3 Prime Time Presenter
Get the latest news from Asia and around the World with Howie Lim and Rachel Kelly on Prime Time on Weekdays 4PM to 7PM. Together with Finance Presenter JP Ong, stay up to date with the latest movements in the Singapore, European and US markets. Learn of the latest trends in property investment and the challenges that Small Medium Enterprises face in a changing economy.
Disclaimer: All analyses, opinions from interviews, recommendations and other information broadcasted, podcasted, published or printed herein are for general information. You should not rely solely on the said information and are advised to seek independent financial advice from your own financial or investment consultant prior to making any investment decisions. Before acting on the information you hear or read on MONEY FM 89.3, remember to consider if it is suitable for your own investment objectives and financial situation. SPH Radio does not accept any liability for any loss whatsoever arising from any use of the information broadcasted, podcasted, published or printed herein.
Watch the previous sessions from Money Matters - Investing & Planning Your CPF For Retirement & Other Life Goals:
Hosted by: MONEY FM 89.3 Finance Presenter Ryan Huang
Guest Speaker: Ivan Guan, Independent Financial Consultant, Founder of SGMoneyMatters.com & Author of the book "FIRE Your Retirement"
Part 1: Investing your CPF - Why and How
Part 2: Planning Your CPF For Retirement & Other Life Goals
Learn the fundamentals of investing and make your money work for you!
Like our Facebook page for more updates on upcoming sessions of Money Matters where our guests share their top tips in helping you build your portfolio and achieve financial freedom.


The change from ISBE Certificates to Educator Licenses is scheduled to occur on July 1, 2013. Those SLPs that have school credentials will be automatically switched. This will be done electronically; you will not be receiving a paper license. It is up to each person to check the ISBE website and make sure he or she is given an Educator License that reflects all current certification.
The legislation that ISBE proposed related to Educator License renewal and the continuing education requirements for different types of Educator Licenses did not pass both houses. Until legislation is passed outlining these requirements, ISBE will be relying on Section 21B-45 of the existing School Code to govern renewal. Section 21B-45 refers to Sections 21-14 and 21-25 for the specific rules regarding continuing education. In both of these sections it states that "a speech-language pathologist or audiologist who is licensed under the Illinois Speech-Language Pathology and Audiology Practice Act and who has met the continuing education requirements of that Act and the rules promulgated under that Act shall be deemed to have satisfied the continuing professional development requirements established by the State Board of Education and the Teacher Certification Board." At this time, ISHA advises all speech-language pathologists and audiologists who hold ISBE certificates to continue to meet the continuing education requirements as outlined by IDFPR and ASHA.
The Legislative and Regulatory Affairs committees will continue to monitor the developments that occur with the Illinois State Board of Education and the Illinois Department of Financial and Professional Regulation and keep the ISHA membership informed.


My storm manifests as a hurricane, a devastating whirlwind of emotion and depression.
It serves as quite an useful metaphor, actually, extending into battening down the hatches, turmoil and wind, emotional destruction.
I find it ironic that I grew up in tornado country, but my demons have taken the shape of a hurricane. But it's helped a bit in therapy to use these metaphors, to help me comprehend what I need to do to heal.
Lately it feels like there's a mental block. A walled off area of emotion that I'd forgotten existed. I keep asking for clarification, because while I understand the words, it doesn't make sense. There's a gap between the knowing and the understanding. I can hear and learn--but I still don't understand.
I think that's what one dream was telling me. I kept not hearing at group therapy sessions (held on a cruise ship, because why?) I kept not knowing what people were saying. "Sorry, I'm deaf," I told them, but even with accommodations I still couldn't hear. Dammit dammit dammit. And then nobody listened to me when I warned them about the hurricane. They couldn't see it. But I could.
Because it's only my storm.
I always batten down the hatches, and try to avoid getting injured by it, but what if I rode it out? Went with the wind? What would it do? I fear the answer.
My task from therapy now is to figure out its name.
The storm roiled in the distance as I sang songs to my daughter last night. She sang along. I can't quite tell if she's mimicking the notes yet, but she has the beat down.
I was 10, I think. We were in our apartment, sitting next to the bunk bed. Mom was teaching me how to sing songs and how to more closely meet the notes, since I was all over the place. She patiently taught me at least to follow the shapes of the notes, even if I couldn't match it. Glo-ooo-ooo-oooria in excelsis De-eo. How to meet the beats.
Hail Holy Queen, enthroned above... Singing songs to my siblings when I put them to bed. Immaculate Mary, your praises we sing... Hearing my mom sing to them as she put them to bed. They sang along sometimes. Was blind, but now I three!
The bedtime routine. "Goodnight," and we get a hug. The hugs stopped when I was around 14. I thought maybe it was an off night--neither of them reached out from the couch to encourage a hug. I tried again for a few nights, before I stopped trying. Why does that bother me so much?
I miss my mom. I miss my siblings.
I kept singing as memories came. Grief. That was the feeling in my heart. The sinking, cold, painful feeling. Grief. I asked the storm, Is that your name?
Parts of it undulated in approval, while I thought this is so stupid at the same time, but it oddly worked. There were more names, I learned, because the rest of it only churned.
But I know one name. Grief.
Grief washed over me as I kept singing. Tears rolled down my face.
Because she's a toddler and because I'm trying to teach her to fall asleep without me, I typically lay silently on the floor for a while until she actually passes out, and then creep out of the room. She's still in the habit of checking to see if I'm still there--but it's less often, and eventually she'll stop. And I'll eventually be able to leave the room while she's sleepy and awake.
When sleep training intersects with trauma. Heh. How many other parents have gone through the same thing?
I sobbed (silently, of course, because no way was I going to interrupt that sleep training).
Pain. My mom disowned me. I lost my siblings. They were like my children. I often ran through the OCD thoughts of how to save them in various calamities--and all of them never involved my parents. Sometimes it involved my brother. But I felt the weight of caring for them. Protecting them, as I learned how to protect myself. Sneaking into their rooms to comfort them. Teaching them tips on how to handle stresses, teaching them that the problem wasn't them, that they weren't bad. It was that dad was ill. And for one brother, how to handle being deaf.
I've already cried so much. Haven't I cried enough? I thought I've done my share of grieving.
But maybe there's more. All the grief and sadness I've bottled up while living at home. Grief over things securely compartmentalized away in my brain that I've forgotten, but it still exists. I felt so much pain.
I learned the term for it the other day. Psychache. I think that's the right term, unless there's another word for it I'm not familiar with. But it's when you are in mental pain and your body hurts like hell. Like you got run over by a truck, like the flu. Thankfully it comes and goes, and is not constant, but Aleve never helps. Nor Tylenol. I've tried.
Maybe it's why I've lost my appetite for the most part. It's grief, and I didn't know it. Maybe my arms ache because I held my little siblings as babies until my arms did ache. Maybe my heart hurts because it was broken when I was disowned.
It took a while for my own baby to fall asleep, and when she did, I crept out quietly, trying not to wake her.
And now I know one of the names.
I am not looking forward to learning the rest.


OK. And we have lift off.
The prizes are in, the hotel is booked, the scenarios are being worked on. All we now need are the players.
We had to ultimately make a choice between two dates, and the overwhelming majority suggested this to be the preference. Huge apologies to anyone who cannot make this date but could make the December one but we had to make the call and the market research we conducted suggested December was just too late in the year and too close to Christmas for many to be able to commit. In terms of preference the vast majority preferred the November date, so here we are.
We've received the prizes from sponsors of the main tournament Bounding Fire Publications (WOW is all I will say here !) and also from sponsors of the Mini Tournaments BattleSchool (WOW, again). Other prizes are also on order.
We'll have our website up and running later in the year.
£15 with an early bird option for anyone paying before end of August of £10.
Payment either in advance via Paypal to boundingfirstfire@gmail.com or pay on arrival at the tournament.
The Headlands Hotel in Blackpool.
Please book directly with the hotel via the number or email address below and ensure that you clearly state that you are attending the ASL tournament as the hotel will be closed to none ASL attendees and their online booking facility will show no rooms available.
Just please get in touch with me should you have any questions or queries.
We are open to any reasonable suggestions (which don't revolve around issues relating to which dice to use....Joe !) and will continue to post updates as we get closer to the tournament both here, by email via the mailing list, Facebook, Boardgamegeek etc.
Please help support this. Intensive Fire historically was THE first and THE major UK tournament. We want to restore it to it's former glory. But we can't do it without YOU the community.
Thanks in advance and hope to see you in November.


London-based college student Natacha Pradere recently flew 3,459 miles to join our growing New York team as a Summer Intern. Currently an Architecture student at the Architectural Association, Natacha also has a personal interest in Engineering and is using a combination of these two passions during her time at Mailjet. We sat down with her this week to catch up about her first few weeks and upcoming projects.
What are you currently doing at Mailjet?
It's been a great first few weeks at Mailjet. From the start, I jumped right in to contribute to a number of projects and sat in on meetings to learn about where our product and our business is headed.
Right now I'm supporting the Developer Relations and Marketing teams on some hackathoninitiatives and a neat social media contest you'll see coming out in a few weeks. I've learned about a number of vibrant tech-startup hubs in the US while researching Hackathon locations. The best part is when I get to apply my learnings from Uni. I've been working on a few smaller web design projects, using my design experience from Architecture school to draw on Adobe Illustrator and picking up Ruby through Codeacademy to build a hardware project!
What is one thing that you've learned about email that you think everyone should know?
I think it's fair to say that before joining Mailjet, I didn't realize the full scope and potential of email. I send and receive email on a daily basis, as both a consumer and a student, but there's so much more that goes into email strategy as a business. Mailjet tools help businesses innovate a form of communication that's been around for ages. Email campaigns going out to a list of 25,000 customers can be customized and analyzed with just a click.
Favorite New York Moment so far?
It's crazy to think that I only landed at Newark airport a few weeks ago. I already feel so accustomed to the culture and way of life here. Still, New York constantly surprises me with stunning views, friendly strangers and the sudden bursts of art you encounter walking through the streets. I love that New York is such a vibrant, busy city but also has smaller corners where you can go to escape the rush. One of my favorite spots is the path along the Hudson River; on a sunny day, you'll see people running, walking and roller skating to the view. I went for a run there last week and was so glad to unwind to such a fantastic sight! The moment was topped off with a delicious New York hot dog!
What advice do you have for other students who are looking to get involved in the startup world?
I would advise them to build a diverse range of experiences, from travelling the world to small summer jobs to interning with a company. Any of these can act as a catalyst to developing soft skills such as communication, teamwork and thinking out of the box.
These skills are especially helpful in the startup environment where there's more accountability and it's constantly fast-paced. For this reason, I recommend everyone to try new experiences. It will help you in your later years. Not to mention that you'll build a wide network along the way, a key element to any profession.


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Food and Farm
Study: Opioid Use Curbed By Colorado Emergency Rooms
By Stephanie Daniel • Jan 26, 2018
Colorado Opioid Safety Pilot Study found opioid usage decreased by 36 percent.
Stephanie Daniel / KUNC
Emergency departments in Colorado have cut back on the use of opioids in a pilot study so successful that it surprised its primary architect.
Ten emergency departments were part of the six-month Opioid Safety Pilot Study overseen by Dr. Donald Stader, associate medical director of Swedish Medical Center's emergency room in Denver. Opioid usage was reduced by 36 percent. That's more than double the expectations researchers had set for the study.
The study followed doctors, nurses and pharmacists who gave patients a less-addictive alternative to opioids (also known as ALTO).
"You could see, at a certain point in October, ALTO's were used more than opioids right. And that's a revolutionary change. You can't miss that point," Stader said. "That's a revolutionary change in how we're practicing medicine."
Opioids include drugs like oxycodone, hydrocodone and morphine. All have been at the center of what health experts say is a dangerous epidemic that has cost many lives.
Stader said alternatives to opioids are a safer way to treat pain than opioids. They include drugs like lidocaine, ketamine and dicyclomine.
The study found that usage of those drugs went up by 31 percent as 35,000 less doses of opioids were dispensed to patients. The study compared opioid and ALTO emergency department prescriptions from June 1 to Nov. 30, 2017 with the same period from 2016.
"Our ALTO treatments went up and our opioid treatments went down and that makes sense because we're still treating pain," Stader said. "We're still treating pain we're just treating it better and safer than ever before in these hospitals."
The participating hospitals represent rural and urban areas and their emergency departments provide acute care, critical access or are freestanding. Over the six-month study, the 10 EDs treated 130,631 patients.
Colorado Students Are 'Curious' About Opioid Epidemic
By Stephanie Daniel • Dec 26, 2017
Karlie Huckles / KUNC
Lesley Pizana, 18, sat at a table in the school library at Colorado Mountain College in Leadville. She was eager to find out more about the opioid epidemic.
"My topic is focusing on the different type of treatments of heroin, opiate addiction," said Pizana.
Colorado Sees Spike In Newborn Opioid Addiction
By Stephanie Daniel • Dec 4, 2017
The opioid epidemic is affecting more and more Coloradoans every year, including the youngest members of our communities: babies.
The Colorado Department of Public Health and Environment said the number of Colorado newborns born addicted to opioids jumped 83 percent from 2010 to 2015. The rate climbed from two births out of 1,000 to 3.6 births in during that five-year period.
Supervised Injection Facility Could Be Coming To Colorado
By Stephanie Daniel • Nov 29, 2017
Jeffrey Beall / Wikimedia Commons
When a safe injection facility was first introduced, Rep. Jonathan Singer was on the fence. Before taking public office, he had worked with people struggling with addiction. This experience made him wary of giving heroin users a place where they could safely inject their drugs.
"The last thing I thought I wanted to do was to encourage them to continue using," he said. "By providing them with a safe space to do that, I thought I might actually be rewarding that behavior that we didn't want to see."
But since then Singer has changed his mind.
Colorado Legislature Tackling Opioid Epidemic In 2018 Session
VIBE 105 / Flickr
In 2018, a bi-partisan group of lawmakers plan to submit several bills to combat Colorado's growing opioid addiction crisis. Hundreds of people in the state have died, and the bills aim to reverse that trend, coving a range of solutions from prevention to intervention to treatment.
The state legislative session starts up in January. Ahead of that, we look at the main aims of six bills.


CG Says: The 2019 Kia Rio drops the base LX hatchback and the top-trim EX models, although most of the EX features are now part of an optional Technology Package. The 6-speed manual transmission has also been dropped. Otherwise, Rio has only minor trim changes following last year's redesign. Rio is a subcompact car offered in two bodystyles, a 4-door-sedan and a 4-door-hatchback that Kia calls a "5-Door". The sole engine choice is a 130-horsepower 1.6-liter 4-cylinder paired with a 6-speed automatic transmission. Available features include Kia's UVO infotainment system with Apple CarPlay/Android Auto connectivity and forward collision warning with autonomous emergency braking. The redesigned Kia Rio is one of the best cars in the subcompact-car segment; it delivers impressive levels of comfort and refinement at attractive prices. It also has good power for the class and comes with a generous warranty.


Built between the 12th and 17th centuries in the Touques River Valley, close to Pont L'Évêque and Lisieux, this ancient medieval fortress is also famous for its remarkable gardens, which has been awarded the Grand Prix EBTS in 2016.
Boutemont was an important fief who reported to the barony of Fauguernon. The Medieval mound erected between the 10th and the 12th centuries is still clearly visible.
The French garden is an extension of the dwelling, it domesticates and orders the nature, according to the principles of geometry, optics and perspective.
© Château de Boutemont 2017, all right reserved.


This classic styled wheel offers vintage Mustang owners a beautiful wheel in sizes ranging from 14x5" to 15x8". The wheel features a brilliant show chrome finish center with Mocha Silver or Charcoal Silver painted windows. As mid-1960s Ford Mustang Wheels continue to get more expensive and harder to find, premium quality reproduction wheels like these are a welcome offering for Mustang restoration projects. Proudly Made in the USA!


Protein can help you shed those unwanted pounds — and keep your belly full. But it's important to eat the right amount and the right kind of protein to get its health benefits.
Protein content: 30-40 gm per 100 gm.
Greek has become such a popular yogurt choice because it has twice as much protein as other types of yogurt. It's also rich in calcium and probiotic bacteria, which is great for gut health. Look for plain Greek yogurt to keep sugar in check.
You could chug watery, flavorless skim milk, or you could enjoy the richer taste of 2 percent while getting a little extra fat to help you absorb the milk's vitamin D and get you closer to your macro targets. Organic milk has the highest nutrient content, including protein and omega.
The underground legume is a fabulous source of protein, and if you steer clear of the roasted and salted varieties, it's a fairly healthy snack. In peanut butter form you'll get around 4gm of protein per tablespoon.


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Q: SAM build in container with environment variables Is there a way to pass environment variables to the container doing the build in:
sam build --use-container

In the sam build documentation, in parameters related to Docker, there is only --docker-network and --skip-pull-image
Use case:
I am using private PyPI repository, and I need to pass credentials as environment variables.
Workaround:
A workaround is:

*

*Pull the docker image used by sam, e.g. lambci/lambda:build-python3.7

*Build a new image with same name & tag

*Run sam build -u with parameter --skip-pull-image
Update 1:
Created a feature request in SAM repo: https://github.com/aws/aws-sam-cli/issues/2144
Update 2:
New parameters were released: --container-env-var and --container-env-var-file in v1.20.0

A: Starting from release v1.20.0 (2021-03-04) you can pass environment variables to the container, either from the command line:
sam build --use-container \
    --container-env-var Function1.GITHUB_TOKEN=<token1> \
    --container-env-var GLOBAL_ENV_VAR=<global-token>

or from a file:
sam build --use-container --container-env-var-file <env-file.json>

Ref: sam build documentation

redpajama_set_name: RedPajamaStackExchange


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Christian Ilić (Friesach, 22 juli 1996) is een in Oostenrijk geboren voetballer met de Kroatische nationaliteit, die bij voorkeur speelt als aanvallende middenvelder.

Carrière
Ilić speelde in de jeugd bij WSV St. Lambrecht, FC Judenburg en SVU Murau. Op 15-jarige leeftijd debuteerde hij in het eerste elftal van WSV St. Lambrecht, een amateurclub op het zesde niveau (Unterliga). In 2012 maakte hij de overstap naar SC Weiz dat twee niveaus hoger uitkwam in de Landesliga. Daar bleven zijn optredens hoofdzakelijk beperkt tot het tweede elftal dat op het vijfde niveau (Oberliga) speelde. Ilić keerde vervolgens terug naar WSV St. Lambrecht waar hij al snel werd opgepikt door TSV Hartberg dat destijds in de 1. Liga uitkwam, het op een na hoogste Oostenrijkse niveau. Op 12 september 2014 maakte de inmiddels 18-jarige Ilić daar zijn debuut in de hoofdmacht, als invaller tijdens een met 1-0 gewonnen thuiswedstrijd tegen SKN Sankt Pölten. Zijn eerste doelpunt maakte hij een seizoen later, na de degradatie naar de Regionalliga, op 31 juli 2015, tijdens een met 5-0 gewonnen thuiswedstrijd tegen SC Weiz, zijn oude club. Met TSV Hartberg dwong hij in 2018 voor het eerst in de clubgeschiedenis promotie af naar de Bundesliga, het hoogste niveau.

Na vijf jaar in Hartberg verkaste de middenvelder eind juni 2019 naar Sepsi OSK. Zijn verblijf in Roemenië was echter van korte duur, toen bleek dat de club niet in staat was om zijn salaris te betalen. Twee weken later tekende de Kroaat een eenjarige verbintenis bij Motherwell. Zijn contract in Schotland werd niet verlengd. Op 21 augustus 2020 tekende Ilić een tweejarig contract bij Lokomotiv Plovdiv. In de zomer van 2021 werd die overeenkomst voortijdig ontbonden en de transfervrije middenvelder sloot vanaf 2 september 2021 aan bij VVV-Venlo voor een proefperiode. Zijn trainingsstage in Venlo werd na een week beëindigd en leidde niet tot een contract.

Statistieken

Beloften

Senioren

1Overige officiële wedstrijden, te weten Steirer-Cup, Scottish League Cup en UEFA Europa League.

Zie ook
 Lijst van spelers van Motherwell FC

Externe links
 Profiel op Transfermarkt.nl
 Profiel op ÖFB.at

Ilić, Christian
Ilić, Christian

redpajama_set_name: RedPajamaWikipedia


JEFFERSON COUNTY, IL (KFVS) - On Friday afternoon, Aug. 14, some residents, the sheriff and officers gathered to see the "In God We Trust" motto placed on the first vehicle.
Todd Ham, the local business owner who donated all the stickers says he decided to do it because he felt it was needed.
""It was a no-brainer just to donate these," Ham said. "Because I think it's great. Everyone is trying to take God out of everything these days. And I just think it's good that Travis and Clint want to put God back in our sheriff's department."
The stickers will be placed on all 12 marked cars.
Sheriff Travis Allen said he will not bow down to the Freedom from Religion Foundation and will continue to stand up for the people of Jefferson County.
"This is our national motto, it's on every bit of our currency, it's important, it's the moral fabric of what our country's made of," Jefferson Co. Sheriff Travis Allen said.
That's why Sheriff Allen said he's putting "In God We Trust" on his squad cars.
The stickers were a decision drawing mixed reaction from the community.
"That's what our country was built on, it's as simple as that," Jefferson Co. resident Jessica Baird said.
"In God We Trust should be on the dollar bill only…not on the back of no police car," said Jerry Gill, of Jefferson Co.
"I personally do believe in God, but I would say that it could be discriminating towards certain people," Carla Moussette said.
Sheriff Allen got the idea from another department in Stone County, Missouri and was surprised by the amount of controversy it received.
"I can't believe that people were so upset about this, it's our country's motto." Sheriff Allen said. "It's on all of our national currency."
Sheriff Allen said all the deputies were on board for the stickers and while he got mostly positive feedback from the community, he knows this idea won't sit well with everyone.
"There's no doubt this will offend somebody," Sheriff Allen said. "My answer to that is that I'm never going to apologize for loving God, loving America and loving the principles this country was founded on. That's why we're all here today."
Jefferson County sheriff, Travis Allen recently received a letter from the Freedom from Religion Foundation urging him to remove the stickers, stating it was inappropriate to place the motto on government property.
But the sheriff says he won't do it.


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Dancin at the Palais
A lovingly designed typographic Riso print celebrating the legendary Dundee dance hall, the Palais. A tribute to one of Dundee's most cherished venues from bygone years – this print is a celebration of the old dance hall and music venue. Taking inspiration from old ads and music posters, this print is a re-imagination of those nostalgic and dazzling typographic designs. This will look fabulous hanging on your walls with its vibrant colours and bold lettering! The Palais opened in the 1920s, creating a dancing boom amongst the people of Dundee. South Tay Street was lined with folk eager for an afternoon tea dance and to swing into the evening dancing up a storm! In the 1960s it transformed into one of the best places to see live music and top artists with their Top Ten Club, playing host to the likes of David Bowie, Bee Gees, Lulu and the Hollies. By the 1970s, the Palais had closed its doors and reopened as Samantha's, before later turning into the club Boomers. Sadly in the 1980s a devastating fire burned the iconic venue to the ground, leaving Dundonians to fondly remember it in its glory days.
© Oh for print's sake 2022


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Higher Education, Research & Innovation After Triggering Article 50
Posted on Wednesday 29 March 2017 Wednesday 29 March 2017
The RSE has joined other National Academies in the UK and Ireland[1] to issue a statement on higher education, research and innovation now that Article 50 has been triggered.
Recognising that innovation is vital for the UK's growth, prosperity and influence—and that higher education and research underpins this—the Academies stress that enhancing the UK's world-leading research, innovation and higher education systems must remain a key priority for the UK Government.
The Academies call for action in 4 areas to ensure that the UK continues to be one of the best places globally for research and innovation:
The UK Government should safeguard the ability of UK institutions to retain and employ EU innovation, research and higher education staff after the UK leaves the EU. Additionally, in order to retain a competitive environment in which to recruit talented researchers, a right to remain should be provided to all EU staff and their dependants, employed in the UK at the time of the departure from the EU.
The UK Government should continue to fully participate in projects such as Erasmus+ and Horizon 2020 until their completion and close association with future European programmes should be fostered.
A target of 3% of GDP should be set for combined public and private R&D spending. Scotland's universities and research institutes are successful in attracting public sector R&D investment (0.92% of GDP in 2014)[2] above the UK (0.55%) and OECD (0.68%) averages. However the overall investment in R&D in Scotland is only 1.6% against the OECD average of 2.4%. An environment which encourages greater private sector investment in UK research and innovation should be cultivated.
The mutual recognition of professional qualifications should be preserved between the UK and EU Member States.
Dame Jocelyn Bell Burnell, President of the RSE said, "Now that Article 50 has been triggered, the National Academies urge the UK Government to commit to championing world class higher education, research and innovation in the UK by putting measures in place to ensure that the UK remains open to the world, welcoming talented people from Europe and further afield."
[1] The Academy of Medical Sciences, British Academy, Royal Academy of Engineering, The Royal Society of Edinburgh, The Royal Society, Royal Irish Academy, The Learned Society of Wales
[2] Gross Investment in R&D Scotland 2014 Tables
RSE responds to Scottish Parliament's consultation on Higher Education Governance Bill
The RSE has responded to the Scottish Parliament's Education and Culture Committee on its proposed Higher Education Governance Bill and has outlined…
National Academies Call for Clear, Open & Meaningful Information on Scottish Independence Debate as they Launch Landmark Book
The RSE and the British Academy (BA) today call for clear, open and meaningful information to be presented to the public…
National Academies & the Law Collaborate to Provide Better Understanding of Science to the Courts
The Lord Chief Justice, The Royal Society and Royal Society of Edinburgh today (11 April 2016) announce the launch of a…
RSE Calls for Review of Proposed APD Reform
The RSE has responded to the Scottish Government consultation on a Scottish replacement for Air Passenger Duty (APD). The Society has…


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The vital role that inositides and their components play in the regulation of cell events – The synthesis and metabolism of Phosphotidylinositol(3,5)bisphosphate
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1.1 Phosphotidylinositol(3,5)bisphosphate: Synthesis and
In the year 1850, Joseph Scherer discovered inositol and determined its empirical formula by its isolation from Liebig's extract of meat. Inositides consist of phosphotidyl-inositol (PtdIns), polyphosphoinositides (PPIns) which are a phosphorylated derivative of PtdIns and inositol polyphosphate(IP). These membrane and cellular components of inositides have been found to play a vital role in the regulation of cellular events (Kangzhen Dong, 2010).
PtdIns, a member of eukaryotic membrane phospholipids, play an important role in phosphorylation of the inositol group in one or more than one place, giving rise to various PtdIns (Corvera et al., 1999). These phosphoinositides are found near the cytoplasmic face. They act as a substrate for various enzymes which convert them into secondary messengers, including PtdIns (3,5) bisphosphate Corvera et al., 1999). These enzymes include phosphoinositol kinase, phospholipase C and phospholipase D (Robinson et al., 1998). The inter-conversions of PPIns are controlled by various lipid phospholipases and kinases. Usually these enzymes will phosphor late or dephosphorylate at a particular hydroxyl group on the inositol ring (Dong., 2010).
Phosphotidyl inositol (3,5) bisphosphate (PtdIns (3,5)P2) is a newly discovered member of PPIns and plays a role in membrane trafficking (Michell et al., 2006), cytoskeletal rearrangement and responding to extracellular environmental changes (Strahl et al., 2007). It is also involved in packing proteins into multivesicular bodies after being ubiquitinated, for growth at high temperatures and for vacuole acidification (Dove et al., 2004).
In 1987, Auger et al. postulated the existence of PtdIns(3,5)P2 but its presence was not confirmed until 1997, when it was isolated and identified in a mouse's fibroblast and in Saccharomyces cerevisiae (Whiteford et al., 1997; Dove et al., 1997). Its presence was also reported in Schizosaccharomyces pombe and in plant cells, suggesting that it exists in all eukaryotes (Dove et al., 1997).
The presence of PtdIns kinase has been observed in various eukaryotic organisms, including yeast, insects and vertebrates. These kinases have been classified into three types: type I/type III PtdIns kinase, type II PtdIns kinase and PtdIns phosphokinase. PtdIns 4 kinase, which is a type II kinase, was the first to be isolated from various mammalian sources and described in detail (Strahl et al., 2004). Later, it was realised that these PtdIns kinase catalyse a reaction on a specific inositol ring (Balla et al., 2006) and were classified according to the product they produce: PtdIns 3-kinase, PtdIns 4-kinase and PtdInsP kinase (see the review of Strahl and Thorner, 2007).
PtdIns are converted to PtdIns 3 phosphate by the action of type III PPIn
3-kinase and then to PtdIns (3,5)P2 by the action of PIPKIII (Michell et al.,2006). In Saccharomyces cerevisiae, VPS34p is responsible for the conversion of PtdIns to PtdIns 3 phosphate. Fab1 catalyses the conversion of PtdIns 3 phosphate to PtdIns(3,5)P2 (Michell et al.,2006). In 2003, Gillooly et al. found that PtdIns (3,5)P2 are synthesised in the endosomal system by the action of type III PPIn 3-kinase, suggesting that PtdIns (3,5)P2 plays a role in membrane trafficking in the endosomal and lysosomal areas of the cell.
The main function of PtdIns polyphosphate in the process of membrane trafficking is to transport the protein to a specific regions of the membrane. VPS34p is localised in the cytosol but can be transported to the endosomal membrane by the action of VPS15p (Stack et al., 1993).
When the vps15 gene mutates in such a way that it can no longer function as kinase, the result is a massive decrease in the production of PtdIns 3P and causes defects in vacuolar protein sorting (VPS). The strains that had a deleted vps15 or vps34 gene displayed common phenotypes (Herman et al., 1992). This suggests that the gene product of these genes may follow the same steps as in vacuolar protein sorting (Stack et al., 1993). Also, overproduction of VPS34p in a strain containing a mutated vps15 gene suppressed the growth and protein sorting of vacuolar protein (Herman et al., 1991).
As previously described, PtdIns are converted to PtdIns 3 phosphate by the action of type III PPIn 3-kinase, VPS34p and then to PtdIns (3,5)P2 by the action of PIPKIII, Fab1p (Michell et al, 2006). The corrective functioning of Fab1 requires three additional proteins which are called the activator proteins of Fab1, Vac14p, Vac7p and Fig4p. The cells lacking these activator proteins show all or the same phenotypic defects as shown by cells lacking the fab1 gene (Dove et al., 2002; Duex et al., 2006).
Fig4p is a PPin phosphatase that dephosphorylates PtdIns(3,5)P2 at the 5th position on the inositol ring and degrades it into PtdIns 3P (Gary et al., 2002). In 2004, Rudge et al. created a recombinant form of Fig4p and found out that Fig4p attacks only PtdIns(3,5)P2 among the other PtdIns. Strains lacking the Fig4 gene had a substantial decrease in the production of PtdIns(3,5)P2, suggesting defective PtdIns(3,5)P2 synthesis. This puzzle was solved in recent studies showing that a large complex regulated the synthesis and degradation of PtdIns(3,5)P2. This is formed by Fab1p, vac14 and Fig4p (Dong, 2010; Botelho et al., 2008; Jin et al., 2008).
The common phenotypes that are associated with the yeast strains lack vac14 or vac7. These are the activators of Fab1p. Strains expressing Fab1p that can no longer function as a kinase, or those lacking the effectors of PtdIns(3,5)P2, have an enlarged vacuole that fills almost all of the cell. This suggests that PtdIns(3,5)P2 is required for the membrane and membrane-bound protein recycling (Michell et al., 2005). An enlarged vacuole is also observed in the vpsΔ cells. It is also observed in Schizosaccharomyces pombe when the ste12 gene has been deleted, which acts as a PIPkIII (Onishi et al., 2003; Takegawa et al., 2003). It was observed in Schizosaccharomyces pombe that the mating response to the mating factors slowed down (Michell et al., 2006). The cells were inefficient in mating, meiosis or sporulation due to the slowing down of the endocytic and exocytic membrane trafficking (Michell et al., 2006). These strains also showed inappropriate sensitivity to stresses like heat. This can be overcome by supplementing the growth medium with an abundance of osmolyte. Osmolyte is non-nutritional and corrects the defects in sporulation (Michell et al., 2006). A possible explanation for these effects is that they are due to defective cell-wall assembly that is caused by faulty membrane trafficking (Michell et al., 2006).
PPIns mediate their role on cellular activities by acting as membrane binding sites for various distinct effector proteins. PROPPIN, a family of effector proteins of PtdIns(3,5)P2, comprises tg18p/Svp1p, Atg21p/ Hsv 1p and Hsv 2p in yeast, which controls membrane trafficking between late endosome, MVB and vacuoles (Michell et al., 2006). In 2004, Dove et al. found out that Atg18p/ Svp1p has a high specificity for binding to PtdIns(3,5)P2 and plays a role in membrane trafficking from the vacuole. It was observed in Atg18pΔ cells that there was an excess of PtdIns(3,5)P2 even when it was not under stress (Michell et al., 2006). The strains containing a mutated form of Atg18p, which could not bind to PtdIns(3,5)P2, were found to have defective membrane trafficking from vacuole to endosome and vice versa (Dove et al., 2004).
In 2003, Fraint et al. found an epsin-like protein, Ent3, that plays a role as an effector protein which has a binding specificity to PtdIns(3,5)P2. The role of Ent3 has been observed in the membrane trafficking of cargo proteins between the trans-Golgi network and the vacuole (Hicke et al., 2003). Under normal conditions or a stressed state, the fusion or fragmentation of a vacuole or lysosome is one of the major functions performed by PtdIns(3,5)P2. Conformational changes in the vacuole can be studied by inducing hypo- or hyper-osmotic shock. These studies will help us to get a clear understanding of the role of PtdIns(3,5)P2 in cellular activities. The cellular levels of PtdIns(3,5)P2 increases with hyper-osmotic shock in Saccharomyces cerevisiae. This has also been observed in other organisms, including plants (Dove et al., 1997; Rugde et al., 2004). While moderate increases in the molecular levels of PtdIns(3,5)P2 was observed under modest stress and little vacuole fragmentation was observed, this could be reversed within ten minutes. However, when extensive stress was induced, a dramatic increase in the levels of PtdIns(3,5)P2 was observed with extensive fragmentation of vacuole. This took 60 minutes to reverse (Duex et al., 2006; Dove et al., 2009; Dong.,2010).
There are three fab1 mutants which help to develop a corresponding relationship between vacuole fragmentation and synthesis of PtdIns(3,5)P2:a fab1 mutant that can no longer function as a kinase (D2134R), had an enlarged vacuole (Gary et al., 1998; Odorizzi et al., 1998); FAB1-5 that produces an extraordinarily large amount of PtdIns(3,5)P2 and had a fragmented or shrunken vacuole; and a fab1 mutant which showed little fragmentation of the vacuole (Gary et al., 1998; Odorizzi et al., 1998) as it maintains only 10% of PtdIns(3,5)P2 levels (Dong.,2010).
1.2 Arrestin: Adaptors for Ubiquitin membrane trafficking
Changes in the cell membrane are brought about by the eukaryotic cells for the correct sensing of- and response to environmental cues. Yeast plasma membranes are remodelled either by degrading or recycling the plasma-membrane transporters by the process of endocytosis. Endocytosis is a mechanism by which the cells change their plasma membrane proteins which help in cell growth and differentiation. Ubiquitination is required for endocytosis which leads to vacuole degradation. In almost of the cases reported to date, Rsp5, a ubiquitin ligase is deployed near the plasma membrane (Hicki et al., 2003).
There are 3 WW domains present on Rsp5 that recognise the PY motif with a specific sequence: PPXY or LPXY (Nikko et al., 2009). Various adaptors have been discovered that take part in ubiquitination of protein including Bsd2 (Hettma et al., 2004), Tre1/2 (Stimpson et al., 2006) and soluble proteins Bul1 and Bul2 (Helliwell., 2001; Soetens et al., 2001). Recent work has found that members of yeast arrestin-like proteins take part in the endocytosis of the metal transporter Smt1 and various amino acid transporters including Can1, Mup1 and Lyp1 under stressed condition or in presence of respective amino acids (Lin et al., 2008; Nikko et al.,2008).
AUGER, K.R., CARPENTER, C.L., CANTLEY, L.C. and VARTICOVSKI, L.,
1989. Phosphatidylinositol 3-kinase and its novel product, phosphatidylinositol 3-phosphate, are present in Saccharomyces cerevisiae. Journal of Biological Chemistry, 264 (34), 20181-20184.
BALLA, T., 2006. Phosphoinositide-derived messengers in endocrine signaling. The Journal of Endocrinology, 188 (2), 135-153.
BONANGELINO, C.J., NAU, J.J., DUEX, J.E., BRINKMAN, M., WURMSER, A.E., GARY, J.D., EMR, S.D. and WEISMAN, L.S., 2002. Osmotic stress–induced increase of phosphatidylinositol 3,5-bisphosphate requires Vac14p, an activator of the lipid kinase Fab1p. The Journal of Cell Biology, 156 (6), 1015-1028.
BOTELHO, R.J., EFE, J.A., TEIS, D. and EMR, S.D., 2008. Assembly of a Fab1 phosphoinositide kinase signaling complex requires the Fig4 phosphoinositide phosphatase. Molecular Biology of the Cell, 19 (10), 4273-4286.
CORVERA, S., 2001. Phosphatidylinositol 3-kinase and the control of endosome dynamics: new players defined by structural motifs. Traffic (Copenhagen, Denmark), 2 (12), 859-866.
DOVE, S.K., COOKE, F.T., DOUGLAS, M.R., SAYERS, L.G., PARKER, P.J. and MICHELL, R.H., 1997. Osmotic stress activates phosphatidylinositol-3,5-bisphosphate synthesis. Nature, 390 (6656), 187-192.
DOVE, S.K., DONG, K., KOBAYASHI, T., WILLIAMS, F.K. and MICHELL, R.H., 2009. Phosphatidylinositol 3,5-bisphosphate and Fab1p/PIKfyve underPPIn endo-lysosome function. The Biochemical Journal, 419 (1), 1-13.
DOVE, S.K., and JOHNSON, Z.E., 2007. Our FABulous VACation: a decade of phosphatidylinositol 3,5-bisphosphate. Biochemical Society Symposium, (74) (74), 129-139.
DOVE, S.K., MCEWEN, R.K., MAYES, A., HUGHES, D.C., BEGGS, J.D. and MICHELL, R.H., 2002. Vac14 controls PtdIns(3,5)P(2) synthesis and Fab1-dependent protein trafficking to the multivesicular body. Current Biology : CB, 12 (11), 885-893.
DOVE, S.K., PIPER, R.C., MCEWEN, R.K., YU, J.W., KING, M.C., HUGHES, D.C., THURING, J., HOLMES, A.B., COOKE, F.T., MICHELL, R.H., PARKER, P.J. and LEMMON, M.A., 2004a. Svp1p defines a family of phosphatidylinositol 3,5-bisphosphate effectors. The EMBO Journal,
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Home > Journals > Chemistry & Materials Science > JBPC
JBPC> Vol.6 No.4, November 2015
Molecular Modeling, Docking and ADMET of Dimethylthiohydantoin Derivatives for Prostate Cancer Treatment
Abstract Full-Text HTML XML Download as PDF (Size:3585KB) PP. 91-117
DOI: 10.4236/jbpc.2015.64010 5,526 Downloads 6,572 Views Citations
Khaled Lotfy1,2
1Physics Department, Faculty of Science, Sohag University, Sohag, Egypt.
2University College of Taiyma, Tabuk University, Tabuk, Saudi Arabia.
In silico technique was applied to screen potential of 16 compounds of 5,5-dimethylthiohydantoin derivatives as androgen antagonist. The 3D structure of the protein was obtained from PDB database. Docking analysis of the compounds was performed using hex docking. Molecular modeling analysis exhibits relatively low LUMO-HOMO energy gap of the studied molecules, indicating that it would be kinetically stable. None of the compounds violated Lipinski's parameters, making them potentially promising agents for biological activities. The title compounds exhibited the lowest docking energy of protein-ligand complex. Finally, the results indicate that these compounds are potentially as an androgen antagonist, and expected to be effective in prostate cancer treatment.
Androgen Receptor, Prostate Cancer, Molecular Modeling, Molecular Docking, ADMET
Lotfy, K. (2015) Molecular Modeling, Docking and ADMET of Dimethylthiohydantoin Derivatives for Prostate Cancer Treatment. Journal of Biophysical Chemistry, 6, 91-117. doi: 10.4236/jbpc.2015.64010.
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text:
Robert Nicholson (1798–1842) was a Northumbrian piper and fiddler. He was the nephew and pupil of William Green, who was piper to the Duke of Northumberland, and was later appointed as his assistant in this role.

He first played in public together with his uncle,  for instance at a meeting of the Society for the Improvement of the English Marygold, in 1816.  However, he was already performing alone at this time; a newspaper article  states that the Duchess's Piper being prevented from playing there by illness,  his young nephew Robert Nicholson, then 18, "just the age of the late famed Wm Lamshaw, when he bore away the prize at a musical match at Elsdon Court Baron" , deputised for him, playing for the first time unassisted. It is clear from this that Green would normally have been expected to play at this event. Again, the following year, at a celebration of Earl Percy's wedding, in North Shields, Nicholson deputised for Green, who said he was unable to attend the event at short notice. It may well be that Green was deliberately excusing himself from these events, so that his nephew would get opportunities to perform in his own right.
He played again in an official capacity that December, at a celebration of the birthday of Lord Prudhoe, in this account he is referred to as assisting "the Duchess's pipers", and called "the Percy piper", suggesting some measure of official recognition from the Duke. He played again for the Society for the Improvement of the English Marygold on various occasions until 1823, together with Green.  An account of their playing for the Society in 1822, stated that "Fitzmaurice, Allen, Lamshaw, or Hair, never performed better"; it also refers to the "present improved form" of the pipes - in 1822 this would probably refer to the keyed instruments developed by Robert Reid. It also confirms that "the revival of northern music... constitutes one of the most prominent objects of the Society."
In 1824, at the Tynemouth Fair in May, "many gentlemen dined at the Northumberland Arms, and were delighted with the ancient music of the Duchess of Northumberland's pipers" - these would have been Green and Nicholson. In William Green's obituary, particular mention is made of their innovative  duet playing, with one playing the air, and the other playing the accompaniment. Previously, the instrument was primarily a solo instrument - harmonies would not have been feasible when the instrument's range was only a single octave, which was the case until the beginning of the 19th century.

Sources for his later life are much scarcer. He was a witness at William Green's marriage in Alnwick, in 1825.  The Duchess's pipers, that is William Green and Robert Nicholson, played at Ovingham Fair in 1826. There seems to be no later dateable reference to him as a piper performing in public.
Green was witness at Nicholson's marriage to Margaret Dodds, in St. Nicholas' Church, Newcastle, in 1831.

Nicholson died in Morpeth, on 11 October 1842, in the Black Swan, in King Street (now called Back Riggs), "unrivalled as a musician on the Northumberland small pipes, and was one of the Duchess of Northumberland's late pipers." In the 1851 census, Margaret Nicholson, a widow, is listed as innkeeper of the Black Swan. As all her children were born before 1842, the identification of her as Robert's widow is very likely. Two years after Nicholson's death, Thomas Chisholm was appointed as piper to the Duke of Northumberland for the Manor of Tynemouth, as his successor in the role.  He performed at several local events in this capacity until 1848, but moved to Newcastle shortly after this.

References

1798 births
1842 deaths
Northumbria
Northumbrian music