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This is the world's most advanced ethical hacking course with 18 of the most current security domains any ethical hacker will ever want to know when they are planning to beef up the information security posture of their organization. In 18 comprehensive modules, the course covers over 270 attack technologies, commonly used by hackers.
Our security experts have designed over 140 labs which mimic real time scenarios in the course to help you "live" through an attack as if it were real and provide you with access to over 2200 commonly used hacking tools to immerse you into the hacker world.
The goal of this course is to help you master an ethical hacking methodology that can be used in a penetration testing or ethical hacking situation. You walk out the door with ethical hacking skills that are highly in demand, as well as the globally recognized Certified Ethical Hacker certification! This course prepares you for EC-Council Certified Ethical Hacker exam 312-50.
In short, you walk out the door with hacking skills that are highly in demand, as well as the internationally recognized Certified Ethical Hacker certification!
Learn more here.
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1001 North Westshore Boulevard, Tampa, FL 33607, United States


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Malaria Course in Tanzania: A Four-Week Postgraduate Course on Malaria Prevention, Control & Elimination
The objectives of the course are to build capacity by reinforcing knowledge and expertise of persons involved in the care of patients, in control programmes or in research activities in the field of malaria and to improve skills in time management, presenting and writing research proposals. At the end of the course, the participants should be able to manage malaria issues more effectively and to develop basic training courses and material in their home institutions.
Structure of the course
The course is offered by Swiss TPH in collaboration with the Ifakara Health Institute (IHI), Bagamoyo Branch and its duration is 4 weeks. The structure is modular and the course is taught using blended-learning approach. Each module lasts one week (5 days). Every Monday, the participants receive questions related to the topic of the week. Under the mentorship of the facilitators and in collaboration with their peers using literature search (internet), the participants complete their assignments and give a presentation to the entire group on Friday. In addition to the self-directed, peer-to-peer learning, the module includes lectures (one per day) and educational visits (one per week). The study time for the 4 weeks is 200 hours of preparational and on-site learning.
International and national experts from affected and non-affected countries selected for their area of expertise, teaching skills and willingness to be deeply involved in the learning process.
Course Dates
Due to the current worldwide increase of COVID-19 cases, the Malaria Course has been postponed. New course dates will be communicated.
Location: Bagamoyo and Zanzibar, Tanzania

subset: commoncrawl


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Whether you're traveling to Missouri to view the Ozark Mountains, rent a boat or jet ski while soaking up the sun on the Lake of the Ozark or practice your golf swing on one of the public golf courses, plenty of family-friendly activities can be found throughout the state. Many of the family resorts in Missouri offer a variety of outdoor activities for guests of all ages and include multiple swimming pools.
Lakeview Resort
Established in 1946, the Lakeview Resort is in central Missouri directly next to the Lake of the Ozarks. The 80 cottages on the property offer one to eight bedrooms with full-kitchens, living rooms, private porches and barbecue grills. An indoor swimming pool, outdoor swimming pool, toddler pool, two playgrounds, volleyball court and outdoor tennis courts add to the entertainment. Additional amenities include laundry facilities, DVD rentals and complimentary Internet access. Water equipment rentals such as boats and waverunners are available at the resort. Lakeview Resort 328 Lakeview Resort Blvd. Sunrise Beach, MO 65079 800-936-5655 lakeview-resort.com
Branson Lakes Family Resort
Nine-miles from Branson, the Branson Lakes Family Resort is within walking distance to the public beach and fishing piers at Lake Taneycomo. Guest rooms consist of cabins that can accommodate two to eight guests and include kitchens, living rooms and picnic areas. RV parking is available at the cabins for an additional fee. Amenities include a playground, kiddie pool, laundry facilities and a game room. The hotel offers panoramic views of the Ozark Mountains. Branson Lakes Family Resort 200 Lake St. Rockaway Beach, MO 65740 417-561-4135 bransonlakesfamily.com
Thousand Hills Golf Resort
The family-friendly Thousand Hills Golf Resort provides cabin and cottage accommodations. Cabins include fireplaces and whirlpool bathtubs while condos offer kitchenettes and living rooms. Pets are allowed to stay in designated condos and cabins for an additional fee. Amenities include an indoor and outdoor swimming pool, 18-hole golf course, outdoor tennis courts, fitness center and hot tub. After a round of golf, stop by Mulligan's Snack Bar, located on the property, where you can purchase beverages and various snacks. Thousand Hills Golf Resort 245 South Wildwood Dr. Branson, MO 65616 417-336-5873 thousandhills.com
Leaf Group is a USA TODAY content partner providing general travel information. Its content is produced independently of USA TODAY.
Photo Credits
- speed boat image by Wimbledon from Fotolia.com
- Attribution: aimee castenell; License: Creative Commons Attribution-Share Alike 2.0 Generic license
- Attribution: Andrew Balet; License: Creative Commons Attribution-Share Alike 3.0 Unported license
- Attribution: Richard from kansas city, united states; License: Creative Commons Attribution 2.0 Generic license
- Attribution: AdamProcter; License: Creative Commons Attribution 3.0 Unported license


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I'm frustrated and disappointed that it has taken so long for Newsday, and voters for that matter, to call out politicians who insist on having their names on signs ["Bravo to less political ego," Editorial, July 31]. It's expensive to keep signs updated.
I've written previously about Nassau County Executive Edward Mangano, within a month or two of his inauguration, having his name associated with everything positive about the county. Permanent signs, such as park entrance signs, feature Mangano's name.
What adds to the waste is the fact that many signs also include the county legislator for the locale, the commissioner overseeing the service, and any town or local official. All these add up to wasted dollars from the taxpayers, most of whom couldn't care less which politicians sponsor a particular site or event.
All officials should follow the example of Brookhaven Supervisor Edward P. Romaine, who is removing his name from town signs and substituting a town phone number for complaints. In fact, all jurisdictions should pass laws to remove individual names from public signs.
Denis O'Driscoll, Westbury


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Webinar JEO Review
Run Unlimited Live And Recorded Webinars With Incredible Performance, Advanced Chat, Attendee Management & Unlimited Seating! What is Webinar JEO ? Product Name: Webinar JEO Webinar Software Product Creator: Walt Bayliss Product Description: Webinar JEO is designed to be a full functioned webinar and live streaming software, allowing you to do 'one to many' style … Read more


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Graduate Research
The Graduate School reserves funding for research travel and the presentation of papers for graduate students whose applications are supported by their faculty. The Department also makes awards from two funds, supported by alumni donations, named for two deceased alumni: the Maura Donohue fund for research travel, and the Stephen Keye Fund for conference travel.
Click here to see a list of recent research projects completed by graduate students.


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solutions manual Cost Accounting :A Managerial Emphasis Horngren Datar Rajan 14th edition
Delivery is INSTANT. You can download the files IMMEDIATELY once payment is done
If you have any questions, or would like a receive a sample chapter before your purchase, please contact us at firstname.lastname@example.com
Table of Contents
Chapter 1. The Accountant's Role in the Organization
Chapter 2. An Introduction to Cost Terms and Purposes
Chapter 3. Cost-Volume-Profit Analysis
Chapter 4. Job Costing
Chapter 5. Activity-Based Costing and Activity-Based Management
Chapter 6. Master Budget and Responsibility Accounting
Chapter 7. Flexible Budgets, Direct-Cost Variances, and Management Control
Chapter 8. Flexible Budgets, Overhead Cost Variances, and Management Control
Chapter 9. Inventory Costing and Capacity Analysis
Chapter 10. Determining How Costs Behave
Chapter 11. Decision Making and Relevant Information
Chapter 12. Pricing Decisions and Cost Management
Chapter 13. Strategy, Balanced Scorecard, and Strategic Profitability Analysis
Chapter 14. Cost Allocation, Customer-Profitability Analysis, and Sales-Variance Analysis
Chapter 15. Allocation of Support-Department Costs, Common, Costs, and Revenues
Chapter 16. Cost Allocation: Join Products and Byproducts
Chapter 17. Process Costing
Chapter 18. Spoilage, Rework, and Scrap
Chapter 19. Balanced Scorecard: Quality, Time, and the Theory of Constraints
Chapter 20. Inventory Management, Just-in-Time, and Simplified Costing Methods
Chapter 21. Capital Budgeting and Cost Analysis
Chapter 22. Management Control Systems, Transfer Pricing, and Multinational Considerations
Chapter 23. Performance Measurement, Compensation, and Multinational Considerations
Please note that the files are compressed using the program Winzip.
Files ending with the extension (.pdf) can be opened using Adobe Acrobat Reader.


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Categories: Music
One of the greatest eras in the history of entertainment, Classic Vegas meets the holiday season head-on. The style, the entertainers, all brought to life and rolled up into your favorite holiday tunes by award winning actor, singer, impressionist, Dean Christopher and his band. A holiday show you soon won't forget. Not to mention a surefire way to get into the holiday spirit.
Copyright © 2020 Regional Arts Commission of St. Louis. All Rights Reserved.


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- Tim Kentley-Klay has been ousted as CEO of high-profile self-driving car startup Zoox.
- Kentley-Klay was voted out by Zoox's board, Bloomberg reported.
- He had no prior experience in cars or artificial intelligence before founding Zoox in 2014 with Jesse Levinson.
The CEO of Zoox has left in a management shake-up at the the high-profile, well-funded, and idiosyncratic self-driving car startup.
Zoox has already started searching for a replacement for Tim Kentley-Klay, who cofounded the Silicon Valley-based company, a source close to Zoox told Business Insider. In the meantime, it has named board member Carl Bass as its executive chairman and cofounder Jesse Levinson as its president, the source said. Bass is the former CEO of Autodesk.
Kentley-Klay confirmed his ouster in a statement posted on his Twitter account. Zoox's board fired him "without a warning, cause or right of reply," he said in the statement.
"Today was Silicon Valley up to its worst tricks," he said. "Rather than working through the issues in an epic startup for the win," he continued, "the board chose a path of fear, optimising for a little money in hand at the expense of profound progress for the universe."
Along with his statement, Kentley-Klay posted a pair of charts comparing Zoox to its chief rivals – Google spinoff Waymo, Uber, and GM-owned Cruise. The charts essentially assert that Zoox has made more progress with its technology for less money than its rivals.
"I came to this town as a founder only to build the future of mobility, and by the metrics shared here was crushing it against the biggest," Kentley-Klay said in his statement.
Bloomberg and the Information previously reported Kentley-Klay's departure. He was voted out by the company's board, Bloomberg reported, citing its own unnamed source. Neither Bloomberg's source nor Business Insider's offered an explanation for the move.
Zoox has raised nearly $US800 million in funding
Zoox has raised some $US790 million in funding to develop an autonomous vehicle. Most recently, it took in $US500 million of funding at a valuation of $US3.2 billion.
In contrast to other companies in the nascent industry, Zoox is working on multiple aspects of self-driving cars, from the software, to the vehicles themselves, to building its own autonomous taxi service. Meanwhile, unlike other companies in the space, Zoox is building cars that are designed to be bidirectional – either end of its cars can serve as the front or the rear.
A native of Australia, Kentley-Klay had no background automobile engineering or artificial intelligence before starting Zoox, according to a recent Bloomberg profile. Instead, he had worked in online advertising.
He became interested in self-driving cars in 2012 after reading a blog post about Google's autonomous vehicle effort, according to the Bloomberg profile. He eventually moved to the US and befriended Anthony Levandowski, then one of the lead engineers on Google's self-driving car project and later the notorious Uber engineer who allegedly stole secrets from Google and passed them on to the app-based taxi company. Levandowski introduced him to Levinson, who at the time was a graduate student at Stanford researching autonomous car technology.
Levinson and Kentley-Klay founded Zoox in 2014.
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The Second District holds that actual injury sufficient to trigger the statute of limitations did not occur at the time a partnership agreement was drafted, but sixteen years later, when the dissolution provision of the agreement was triggered or when plaintiffs began to incur legal fees in response to a third party's attempt to dissolve the partnership under the terms of that agreement.
Robert and Oliver Inge founded the Inge Realty Company. In 1988, they retained Gibson, Dunn & Crutcher to advise them regarding restructuring the company to minimize income tax liabilities and implement a succession plan that would ensure that Inge Realty remained a family-run enterprise after they could no longer run the business. Gibson, Dunn recommended a limited partnership and drafted the partnership agreement.
A dispute arose after Oliver died in 2003. The Bank of the West, as executor of Oliver's estate, initiated a probate action that ultimately sought, among other things, dissolution of the partnership under the terms of the partnership agreement because Robert was disabled or incompetent to run the business, leaving no general partner to run the business. The partnership agreement appeared to require dissolution of the partnership in such circumstances. The parties to that action reached a settlement in November 2005 that was confirmed by the court in December 2006.
After entering into multiple tolling agreements beginning in 2004, the Robert Inge family members sued Gibson, Dunn for legal malpractice arising out of the firm's drafting of the partnership agreement. The trial court granted Gibson, Dunn's motion for summary judgment, ruling that statute of limitations expired no later than 1992, four years after the legal services were completed.
The Court of Appeal disagreed with the trial court's conclusion that actual injury under Code of Civil Procedure § 340.6, the statute of limitations applicable to legal professionals, occurred upon execution of the partnership agreement. The agreement lacked a succession plan in the event of the retirement or incapacity of the surviving partner. This created only a potential for harm, not actual injury. Actual injury occurred either when Robert's disability triggered the dissolution provisions of the agreement, or when plaintiffs incurred legal fees to respond to Bank of the West's attempt to dissolve the partnership. Because of the tolling agreements, it was immaterial which of these events constituted the first instance of actual injury.
The Court of Appeal also rejected Gibson, Dunn's argument that the payment of fees by Inge Realty to Gibson Dunn at the time the agreement was drafted, without more, was sufficient to trigger the running of the limitations period. The clients received substantial value from the firm's work, and the theoretical cost of hiring a new attorney to draft a succession plan was merely hypothetical rather than "actual" injury. At a more fundamental level, it would nullify the tolling provisions of CCP § 340.6(a)(1) to hold that actual injury is sustained at the time legal fees are paid to the allegedly negligent attorney.
Finally, whether or not the plaintiff seeks to recover an item of damages, such as fees paid to the negligent attorney, does not change the date it sustained actual injury for purpose of the statute of limitations.
Comment: Although the Court reiterated that the statute of limitations begins to run as soon as the plaintiff suffers actual injury, it makes clear that potential harm does not constitute actual injury. This decision could have significant impact on transactional attorneys drafting documents designed to be effective for many years.


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Wallpaper can add a touch of sophistication and style to your decor, but this is immediately compromised when there are loose seams, punctures, or trapped air bubbles. Fortunately, there are some simple ways to repair your wallpaper and restore its impressive aesthetics.
Peeling Seams
The vertical seams between your strips of wallpaper can become loose for a number of reasons. Whether it is because the factory-applied adhesive on your prepasted vinyl didn't stick, the glue was squeezed from the seam when the paper was rolled flat, or the paper has suffered some bumps, the repair process is the same.
You'll need a small artist's brush to spread an even coat of wallpaper seam adhesive on the underside of the exposed seam. Use a wooden seam roller to flatten off the seam before you use a damp sponge to clean off any excess adhesive.
If your loose seam has a horizontal tear, you'll need to roll the tear flaps back into their original position. You should line up the top piece with the decorative pattern over the bottom flap to hide the backing paper.
Punctures or Rips
A severe puncture or rip will mean that you'll need to cut out the damaged area and install a wallpaper patch. You will need a section of matching wallpaper, so if you don't have any from the original install, you'll need to buy a small sample from a wallcovering store. If you cannot find the pattern, you'll need to take a piece from a hidden area such as inside a closet.
The best way to make an almost invisible repair is a double cut patch. You should tape the patch over the damaged area to align the pattern perfectly with the wall. Just be aware that wallpaper will stretch a little after it has been wet, so if the pattern doesn't precisely line up, don't panic.
When the patch is taped in place, use a box cutter or razor edge to cut through both paper layers. Use a straightedge to get clean lines and cut through completely at each corner. Untape the patch and put it to one side.
Carefully peel the section of damaged paper off your wall. It may leave some backing that should be removed using a slightly damp sponge. Repair any divots in the drywall using a spackling compound. Once this is dried, you can apply the patch to the wall; just be sure to align the pattern carefully before you smooth the area.
Trapped air causes bubbles and blisters that are often a result of installation problems. You'll need to release the air and reglue the paper. You can use a razor knife to cut an X through the paper and remove any particles that may be causing the blister. Another option is to use a glue injecting syringe that can be pushed directly into the bubble. Once the adhesive is injected in, you can use a steam roller to flatten the repair.
Repairing wallpaper can save you the costly process of redecorating, but it does require a little care and attention. So, be prepared to take your time, and you should enjoy the best results.


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IT TAKES a brave soul to race to the rescue of a stranded great white shark.
There are those teeth for one thing - large and sharp enough to take off a man's helping hand, even out of the water.
But Andrew Eckersley didn't think twice last Friday morning when he spotted one of the fearsome predators washed up on a beach on the Mid-North Coast in New South Wales.
Mr Eckersley and a lone surfer rushed to the 3m shark's aid, treating it with the kind of care and compassion usually reserved for beached whales.
"It was pretty scary at first. This guy in a wetsuit was sort of baling water on to its back by hand and digging out a hole for it on the ocean side," Mr Eckersley said yesterday.
"It was pretty big. I wouldn't have been able to put my fingers together if I was giving it a cuddle."
Using logs they found on the beach, the pair tried levering the shark out of the sand to get it into deeper water.
"There was the thought while we were getting the logs under it that I might pinch it or something and it would lunge at me," he said.
Thankfully, it didn't, but the logs failed to free it from the sand, so the pair tried gently pulling the beast out to sea, "inch-by-inch".
"We got it out to about mid-thigh depth and it was starting to perk up again, which was exciting," Mr Eckersley said.
"I think the other guy started to get his confidence up a bit when he realised it wasn't going to bite our legs off, so he took it out a bit further."
Photographer Ruth Fahey, who captured the remarkable rescue on Hungry Head beach, said she first thought the maneater was a stranded dolphin.
"Then I got closer and saw it was this huge shark and just thought, 'Holy crap!'," she said.
Once it got to deeper water the shark slowly started to recover and disappeared beneath the breakers, heading out to sea. But sadly, it was discovered dead on the same beach the following day.
Its jaws had been hacked out by someone as a souvenir, an illegal practice in NSW.
Sydney Aquarium aquatic biologist Sebastian Schmid said it was "very unusual" for a live great white to wash up on a beach and suggested it was already sick when it first came ashore.


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Humane Society of Noble County, Inc.
1305 Sherman Street
Kendallville, Indiana 46755
Phone: 260-347-2563
The Humane Society of Noble County is dedicated to providing assistance to homeless and abandoned pets. My name is Jennifer, I am the executive director, and I do a lot of everything! I have a small staff caring for an average of 200 animals on any given day. All of us are very passionate about what we do. We believe we offer a wonderful organization to our community. We are fierce advocates for homeless pets, for spaying and neutering and for helping both pets and the people that own them.
Adopt a pet from Humane Society of Noble County, Inc.
Directions and map
Note: PO Boxes will not show correctly on the map below.


text: Is anyone getting disconnected today more than usual? I am always NAT type good, yet today i have been disconnected 80% of games today, NOT exaggerating. I had that same problem a lot of people yesterday had with the "unable to sync achievements" thing, and then had red NAT type for the first time ever. At this point today i haven't played a game that hasn't disconnected me in over 2 hours............ I am completely speechless..... Wondering if anyone is experiencing this?


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Unclaimed $1.5m lotto ticket sold at Gladstone news agency
GLADSTONE has a new millionaire, and he or she doesn't even know it yet.
Park Street News & Gifts sold a quick pick in Saturday's division one $22 million Lotto Superdraw which has won $1,571,428, the second winning ticket sold at the news agency in three months.
It's now one of the city's luckiest news agencies after it sold a winning ticket worth $1.1 million on March 20.
>>Couple wins $1.1 million, plan a 'quiet celebration'
Aaron Cameron, co-owner of the business, said he waited three years before sell a winning ticket, but it's exciting they are now rolling in and he hopes they keep coming.
He said a much wider pool of customers throw down a bet in the Superdraw, meaning it could be anyone, including outside of their regular customer base.
"With Superdraws you do get an influx of customers, not your typical person who plays every night," he said.
"But we will be happy if it's a regular customer needing the money.
"There's not many businesses where you can make someone a millionaire overnight, and change their life."
Golden Casket, the news agency chain which Park Street News is a part of, is expected to release more details about the winning ticket shortly.


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Cassandra d'Avespeare
Cassandra d'Avespeare was the wife of Urien d'Avespeare. She is the daughter of Macaire d'Garron. She is very close with her father.
She was born during an eclipse, which is often seen as an omen of magical presence.
This pairing was very controversial, as Cassandra was a godsworn forsaking her vows for the union.
page revision: 5, last edited: 26 Jul 2013 20:29


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What Man of Many Readers Bought in September 2019
Our loyal readers (hey, that's you!) are savvy shoppers with an eye for the best in modern style, gear, and gadgetry. Meanwhile, September is a great month for new releases and new deals alike. Putting all these elements in one place, we've compiled a list of products that our readers bought in September 2019.
Prepare yourself for quality EDC, a book on mechanical watches, a hand-crafted wetsuit, and more. We've brought you various discoveries in the past, but this time around, you're the curator of choice products. In fact, it looks like we've got some shopping to do ourselves.
Flatrock Sarvo Series 3x2mm Full-Length Steamer
When only the best wetsuit will suffice, accept nothing less than the Sarvo Series from Flatrock. Each one is hand-crafted from 18 panels of Japanese limestone neoprene, resulting in the utmost tier of comfort and versatility. Features include an ezy-glide chest zip for easy entry, soft inner lining, and increased neoprene thickness around the core.
Consider us completely unsurprised that Aussies have been buying this thing in droves.
KA-BAR Knives, Inc Mark 98 Folder
Between its blade of 5Cr15 Stainless Steel and multi-coloured G10 handle scales, the Mark 98 makes for a brilliant folding knife. It opens with a flipper and can be carried either tip up or tip down. Throw in a great price and a lightweight profile and you have yourself some impeccable EDC.
Corkcicle Whiskey Wedge
No one argues with a cold and delicious Old-Fashioned and that's why the Whiskey Wedge is such a perennial hit. Included in the package is an Old-Fashioned whisky glass and silicone ice form. To use, insert the silicone ice form into the glass and freeze water inside the form.
You get a firm and robust wedge of ice in return, which will keep your Old-Fashioned (or any cocktail) cold but not watered down. The best part? This thing actually works.
The Wristwatch Handbook: A Comprehensive Guide to Mechanical Wristwatches by Ryan Schmidt
Within the pages of this elegant hardcover book is pretty much everything a watch lover could ask for. That includes over 470 colour photographs along with an endless supply of information, all of which brings a veritable bounty of classic timepieces to life. It comes to us from Ryan Schmidt, who spent over a decade researching mechanical watches around the world.
Whether you're a curious novice or seasoned enthusiast, you'll find plenty to relish.
Ashcroft Twist Whiskey Glass Set
As it turns out, Man of Many readers are big fans of whisky. We're definitely not here to judge, hence our copious amounts of whisky coverage. That brings us to the Twist Whiskey Glass Set from Ashcroft Fine Glassware. Made of top quality lead-free crystal, each glass delivers a truly eye-catching aesthetic.
Plus, it holds up to 10 oz. of whisky. What's there not to love?
SUUNTO Core All Black Military Men's Outdoor Sports Watch
We featured the SUUNTO Core on last year's list of the 20 Best Tactical Watches, and it hasn't lost one iota of its allure in the time since.
Aimed squarely at outdoor types (and military personnel), it hosts an altimeter, compass, barometer, weather indicator, and more. Get it in black and take to the wilderness in style.
Midori MD Notebook – A5 Grid Paper
Formerly included on our list of the 11 Best Notebooks that Aren't Moleskin, the Midori MD Notebook hails from Japan and comes filled to the brim with creamy A5 grid paper. Bursting with quality, the paper delivers no bleed-through whatsoever, regardless of what kind of pen or pencil you're using. Our readers have discovered the difference and so should you.
You'll also like:
Amazon Finds May 2019 – Home Improvement
Amazon Finds June 2019 – The Gamer
Amazon Finds July 2019 – The Book Worm


text: Online audio converter to AC3 Add audio/video files Click here to choose files or Drop them hereUp to 50 files#Source fileSizeStatus Sample rate: do not change1000 Hz8000 Hz11025 Hz16000 Hz22050 Hz24000 Hz32000 Hz44100 Hz48000 Hz96000 Hz Channels: do not changemonostereo Normalize Automatically start I consent to collecting, storing and processing my data from this form according to Privacy Policy and Terms of Use.ConvertAC3 is considered as the main format of movies audio, DVD, HD DVD and Blu-ray Disc. Using it creates some truly high-quality soundtracks, with multichannel surround sound. Particularly pronounced features of the format are manifested when listening to the recordings on the subwoofer.If you need to get an audio file in AC3 format, then nothing prevents you to use the free online audio Converter to get the output audio track, able to delight even the most experienced music lover. As source you can use almost anything, such as MP3 to AC3, WAV to AC3, FLAC to AC3 and even ACC to AC3.


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"Triton's daughter will be mine, and then I'll make him writhe. I'll see him wriggle like a worm on a hook!" -Ursula.
Ursula the Sea Witch (voiced by Pat Carroll) is main antagonist of Jaden meets The Little Mermaid. Ursula was once a member of the kingdom of Atlantica until King Triton banished her for her wicked ways. She tried to take over oceans by using Ariel to her advantage. She did it by making a deal with Ariel. Ursula would turn Ariel into a human for three days so that she could be with the prince of her dreams, Eric. If Ariel could get Eric to kiss her before the sun set on the third day, Ariel would remain human permanently, but if she couldn't, she'd turn back into a mermaid and belong to Ursula. All Ariel had to pay in exchange for this was her voice! Ariel took her offer, and became a human. When Ariel was closed to kissing Eric, Ursula took drastic measures and disguised herself as a human named Vanessa and put Eric under a spell to have him marry her instead of Ariel. But she was defeated by both Eric and Jaden.
- Ursula will return for revenge in Jaden's Adventures of Help! I'm A Fish.
- She will guest star in Jaden and The Muppets (2011), as one of Set's minions to try to break up Jaden and the gang.
- Ursula will also be one of many villains to try to destroy Jaden, Mickey Mouse, and friends in Jaden's Adventures of Fantasmic!
- Ursula will become Jeffrey's enemy in Jeffrey & Friends meet The Little Mermaid.
- Ursula will appear with the villains in Jeffrey & Friends in Fantasmic!.
- Ursula becomes Juniper Lee's enemy in episode 7 of Juniper Lee's Adventures Series titled Mermaid Summer.
- Ursula will become Sly Cooper's enemy in Sly Cooper meets The Little Mermaid.
- Ursula will become Ed, Edd and Eddy's enemy in The Eds' Adventures of The Little Mermaid.
- Ursula will become Twilight's enemy in Twilight meets The Little Mermaid.
- In Descendants 2, Ursula will have a daughter named Uma (portrayed by China Anne McClain).


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'The Hunger Games' is Heading to the Stage - Find Out When You Can See It Here!
The Hunger Games movies may be coming to an end in November 2015 — but it's definitely not going to be the end of the franchise.
In the summer of 2016, The Hunger Games will be turned into a live stage performance in London, according to an announcement released by Lionsgate.
"Robin de Levita and the entire production team are the perfect partners for extending The Hunger Games franchise into a live theatrical experience," Lionsgate Chief Marketing Officer Tim Palen said in the announcement. "Their creative genius, combined with world-class production values and state-of-the-art technology will provide a uniquely immersive experience for fans around the world."


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Insulin signaling through Akt/protein kinase B analyzed by small interfering RNA-mediated gene silencing
Communicated by C. Ronald Kahn, Harvard Medical School, Boston, MA, May 2, 2003 (received for review December 24, 2002)
Glucose homeostasis is controlled by insulin in part through the translocation of intracellular glucose transporter 4 to the plasma membrane in muscle and fat cells. Akt/protein kinase B downstream of phosphatidylinositol 3-kinase has been implicated in this insulin-signaling pathway, but results with a variety of reagents including Akt1–/– and Akt2–/– mice have been equivocal. Here we report the application of small interfering RNA-directed gene silencing to deplete both Akt1 and Akt2 in cultured 3T3-L1 adipocytes. Loss of Akt1 alone slightly impaired insulin-mediated hexose transport activity but had no detectable effect on glycogen synthase kinase (GSK)-3 phosphorylation. In contrast, depletion of Akt2 alone by 70% inhibited approximately half of the insulin responsiveness. Combined depletions of Akt1 plus Akt2 in these cells even more markedly attenuated insulin action on glucose transporter 4 movements, hexose transport activity, and GSK-3 phosphorylation. These data demonstrate a primary role of Akt2 in insulin signaling, significant functional redundancy of Akt1 and Akt2 isoforms in this pathway, and an absolute requirement of Akt protein kinases for regulation of glucose transport and GSK-3 in cultured adipocytes.
Insulin is a key regulator of glucose homeostasis, and its absence is lethal in humans. The ability of insulin to lower blood glucose stems in part from its actions in muscle and fat to enhance sugar uptake through regulation of glucose transporter 4 (GLUT4) (for a recent review, see ref. 1). These transporters are sequestered in perinuclear membranes in unstimulated cells and are rapidly induced to recycle to the plasma membrane in response to insulin (2). Insulin signaling through its receptor tyrosine kinase mediates a phosphatidylinositol 3-kinase-dependent pathway that produces the phosphatidylinositol (3,4,5) trisphosphate required for this effect (for review, see refs. 3–5). Among the downstream effectors strongly implicated in linking this signaling pathway to components that regulate GLUT4 trafficking is the protein kinase Akt (also known as protein kinase B) based on studies with cultured cells and a gene knockout mouse model (6–10). However, this important issue has been controversial (11), and recent data from mice lacking the Akt1 isoform showed no compromise in insulin sensitivity (12). Skeletal muscle from mice deficient in Akt2, the predominant isoform expressed in muscle and fat, is only modestly less sensitive to low levels of insulin and actually responds normally to maximal doses of the hormone (10). The diabetes observed in these mice may be largely due to the dramatic attenuation of insulin action on liver gluconeogenesis (10). Although gene-specific knockout mice provide an excellent tool to study acute actions of signaling molecules, it is possible that phenotypes observed in mice may result from unrelated changes in gene expression and developmental regulation. No data on insulin signaling in isolated primary or cultured adipocytes lacking Akt1 or Akt2 have been published.
Here we have addressed this issue by selectively inhibiting the expression of Akt protein kinases in intact cultured adipocytes through the use of interference RNA (for reviews see refs. 13 and 14). This powerful approach overcomes the problems encountered in mouse gene knockouts where loss of both Akt1 and Akt2 genes is lethal. First discovered in Caenorhabditis elegans (15), this gene-silencing technique uses double-stranded RNA to activate nuclease-containing protein complexes (RNA-induced silencing complex) to target a specific mRNA species, which is then degraded (16, 17). Before insertion into protein-silencing complexes, processing of double-stranded RNA into small interfering RNA (siRNA) duplexes of 21–23 nt occurs by enzymes known as Dicers (18–20). Extension of the technique to mammalian cells has involved the use of synthetic siRNA duplexes of 21-base lengths transfected directly into cultured cells (21), where decreased levels of selected proteins can be observed in response to siRNA after 24–72 h (21). We report here the details of a method that can be used successfully to silence genes in insulin-sensitive cultured adipocytes and show that virtual complete ablation of Akt1 and ≈70% depletion of Akt2 can be achieved. Combined depletion of these Akt isoforms largely attenuates insulin signaling to both GLUT4 glucose transporters and glycogen synthase kinase (GSK)-3, demonstrating an obligatory role of Akt protein kinases in these insulin-signaling cascades.
Materials and Methods
Materials. Human insulin was obtained from Eli Lilly. Goat polyclonal anti-Akt1 Ab (antigen human Akt1 peptide near C terminus, sc-7126), horseradish peroxidase-conjugated donkey anti-goat IgG, mouse monoclonal anti-lamin A/C (sc7293), monoclonal anti-GSK-3α/β, and polyclonal anti-protein kinase C (PKC)λ/ζ (C-20, sc216) were from Santa Cruz Biotechnology. Rabbit polyclonal anti-Akt2 Ab (antigen peptide at C-terminal of human Akt2) was kindly provided by Morris J. Birnbaum (University of Pennsylvania, Philadelphia). Rabbit polyclonal Ab against adipocyte complement-related protein of 30 kDa (Acrp30) was from Affinity BioReagents (Golden, CO) and Ab against nonmuscle myosin IIB was from Covance (Richmond, CA). Polyclonal Abs against phospho-Akt Thr-308/309, phospho-GSK-3α/β (Ser-21/9), and phospho-Erk-1/2 were from Cell Signaling Technology (Beverly, MA). Monoclonal phosphotyrosine Ab (4G10) was from Upstate USA (Charlottesville, VA). The FITC-conjugated goat anti-mouse was from Bio-Source International (Camarillo, CA). The plasmid expressing Myc-tagged GLUT4-EGFP was constructed as described (22).
Design and Synthesis of siRNA Duplexes. The 21-mer sense and antisense strands of RNA oligonucleotides were designed as described (21). The RNA oligonucleotides were synthesized in the 2′-ACE(TM) protected form, which enhances overall RNA stability and resistance to nucleases. The complementary sense and antisense strands of RNA oligonucleotides were mixed, 2′-deprotected, annealed, and purified by PAGE. Gel-purified duplexes were subsequently desalted by using reverse-phase column chromatography, followed by washing with 75% ethanol twice to ensure complete salt removal and dried by use of a Speed-Vac. The pellets were resuspended in nuclease-free water before transfection into cultured cells.
Cell Culture and Electroporation of 3T3L1 Adipocytes. The 3T3-L1 fibroblasts were grown in DMEM supplemented with 10% FBS, 50 μg/ml streptomycin, and 50 units/ml penicillin and differentiated into adipocytes as described (23). The 3T3-L1 adipocytes were transfected with siRNA duplexes by electroporation. In brief, the adipocytes at day 5 of differentiation were detached from culture dishes with 0.25% trypsin and 0.5 mg of collagenase/ml in PBS, washed twice, and resuspended in PBS. Approximately 5 million cells (half of the cells from one p150 dish) were then mixed with siRNA duplexes, which were delivered to the cells by a pulse of electroporation with a Bio-Rad gene pulser II system at the setting of 0.18 kV and 960 μF capacitance. After electroporation, cells were immediately mixed with fresh medium for 10 min before reseeding onto multiple-well plates designed for the deoxyglucose uptake assay, Western blotting, and immunofluorescence microscopic analysis.
Immunofluorescence Microscopy. To visualize lamin A/C, cells were fixed with 4% formaldehyde and permeabilized with PBS containing 1% FBS and 0.5% Triton X-100. Cells were then incubated with primary mouse anti-rat lamin A/C Ab for overnight at 4°C. After washing, cells were incubated with FITC-labeled goat anti-mouse IgG for 30 min at room temperature. To analyze GLUT4 translocation in adipocytes, cells were cotransfected with Myc-GLUT4-EGFP plasmid and siRNAs by electroporation. After this, adipocytes were serum-starved, treated as noted in the figure legends, washed, and immunostained by using the procedure described (22). In brief, the cell surface Myc-GLUT4-EGFP was visualized with mouse anti-Myc Ab and rhodamine-labeled anti-mouse secondary Ab. After washing, the coverslips were mounted in 90% glycerol containing 2.5% diazabicyclo[2.2.2]octane. Fluorescence microscopy was carried out with a IX70-inverted microscope (Olympus, Melville, NY) with charge-coupled device camera (Roper Scientific, Trenton, NJ) and metamorph image processing software (Universal Imaging, Downington, PA).
Western Blotting. After experimental treatments, the cells were solubilized as described (22). To detect phosphorylation of Akt Thr-308/309, GSK-3α/β Ser-21/9, and tyrosine phosphorylation of Erk-1/2, 50 μg protein from 3T3-L1 adipocyte lysates were resolved with 8% SDS/PAGE and electrotransferred to nitrocellulose membranes, which were incubated with anti-phospho-specific Abs (1:1,000 dilution) overnight at 4°C and then with horseradish peroxidase-linked anti-rabbit IgG Abs (1:10,000 dilution) for 1 h at room temperature. Tyrosin phosphorylation of insulin receptor substrate (IRS) proteins was detected with monoclonal phosphotyrosine Ab followed by horseradish peroxidase-linked anti-mouse IgG Abs. Akt1 was detected with primary goat polyclonal Ab (1:750 dilution) and secondary horseradish peroxidase-linked donkey anti-goat Ab (1:10,000 dilution). Primary rabbit polyclonal Abs against Akt2 (1:1,000 dilution), nonmuscle myosin IIB (0.1 μg/ml), Acrp30 (0.5 μg/ml), and PKCλ/ζ (1:500 dilution) were used to detect their antigens by using 25 μg of protein from total cell lysates. The membranes were washed with wash buffer (PBS, pH 7.4/0.1% Tween 20) for 1 h at room temperature after incubation with each Ab. Finally, the levels of target proteins or phosphorylated proteins were detected with an enhanced chemiluminescence kit. To use the same nitrocellulose membrane to detect several proteins and phospho-proteins, the blots were incubated with gentle shaking in stripping buffer (62.5 mM Tris·HCl, pH 6.7/100 mM 2-mercaptoethanol/2% SDS) for 30–45 min at 60°C and washed for at least 1 h with wash buffer before reblotting with the Ab designed for the next experiment.
The 2-Deoxyglucose Uptake Assay. Insulin-stimulated glucose transport in 3T3-L1 adipocytes was estimated by measuring 2-deoxyglucose uptake. In brief, siRNA-transfected cells were reseeded on 12-well plates and cultured for 40 h and then washed twice with DMEM before incubation with DMEM containing 0.5% BSA for 4 h at 37°C. Cells were then washed twice with Krebs–Ringer's Hepes buffer (130 mM NaCl/5 mM KCl/1.3 mM CaCl2/1.3 mM MgSO4/25 mM Hepes, pH 7.4) and further starved for 1.5 h with Krebs–Ringer's Hepes buffer supplemented with 0.5% BSA and 2 mM sodium pyruvate. Cells were then stimulated with insulin for 30 min at 37°C. Glucose uptake was initiated by addition of [1,2-3H]2-deoxy-d-glucose to a final assay concentration of 100 μM for 5 min at 37°C. Assays were terminated by four washes with ice-cold Krebs–Ringer's Hepes buffer, and the cells were solubilized with 0.4 ml of 1% Triton X-100, and 3H was determined by scintillation counting. Nonspecific deoxyglucose uptake was measured in the presence of 20 μM cytochalasin B and subtracted from each determination to obtain specific uptake.
Results and Discussion
siRNA-Induced Gene Silencing in Cultured Adipocytes. To test whether siRNA can induce gene-specific silencing in adipocytes, we first targeted the gene encoding lamin A/C, previously shown to be sensitive to this technique in other cells. Cy3-tagged 21-nt siRNA duplexes directed against mouse lamin A/C mRNA were designed and synthesized (Fig. 1A). The initial experiments we performed showed that conditions developed for siRNA-mediated gene silencing in other cells types (21) worked well in 3T3-L1 fibroblasts (Fig. 1BRight), but failed to work in 3T3-L1 adipocytes (not shown). We therefore developed alternate methodology to transfect lamin A/C siRNA into 3T3-L1 adipocytes by using electroporation. With this method, Cy3-siRNA was introduced with virtually 100% efficiency into the cultured adipocytes, and by 48 h nearly all cells showed loss of nuclear lamin A/C compared to cells transfected with a scrambled Cy3-tagged siRNA species (Fig. 1B). Quantification of these results showed that adding 20 nmol of siRNA to a suspension of 5 × 106 adipocytes results in loss of lamin A/C in ≈90% of the adipocytes with no detectable toxicity (Fig. 1C). These findings provide the basis for reliable gene silencing in insulin-sensitive cultured adipocytes.
Two siRNA species directed against each of the Akt isoforms Akt1 and Akt2 were then tested for their abilities to inhibit expression of these protein kinases in 3T3-L1 adipocytes (Fig. 2). Each of the Akt1-directed siRNA species inhibited expression of Akt1 protein at both 24 and 48 h after transfection. One of these (akt1b) directed virtually total ablation of Akt1 expression by 48 h, whereas Akt2 expression was unaffected (Figs. 2B and 3 A and B). Similarly, Akt2 expression could be selectively attenuated by ≈70% after transfection of the siRNA species akt2b, whereas the akt2a siRNA was less effective (Figs. 2B and 3 A and B). Interestingly, the akt1b and akt2b siRNA species that show most efficacy are targeted to similar regions of the Akt1 and Akt2 mRNA sequences that encode amino acids 351–357 and 352–358 in Akt1 and Akt2, respectively (Fig. 2 A). Whether the secondary structure of this Akt mRNA region is particularly susceptible to siRNA-directed RNA degradation requires further study. The selectivity of akt1b vs. akt2b siRNAs to silence their respective target mRNA species is apparent even though only 4 of 21 nucleotides are different (Fig. 2 A). Expression of several other unrelated proteins (e.g., myosin IIB shown in Figs. 2, 3, and 5 and adipocyte-specific protein Acrp30 shown in Figs. 3 and 5) were also unaffected by akt1b or akt2b siRNAs.
Differential Effects of Akt1 and Akt2 Gene Silencing on Insulin Signaling. Akt1 and Akt2 are phosphorylated and activated by the protein kinase PDK1 at Thr-308 or Thr-309, respectively, in the activation T-loop, and further activation occurs through phosphorylation at Ser-473 or Ser-474, respectively (24–26). The effects of selective loss of Akt1 vs. Akt2 proteins on insulin-stimulated phosphorylation of total Thr-308/309 contained in both proteins were assessed by Western blotting with an anti-phospho-Thr-308/309 Ab. Total loss of Akt1 protein resulted in only a 10–20% reduction in total Thr-308/309 phosphorylation of Akt protein kinases in cultured 3T3-L1 adipocytes, consistent with previous results showing Akt1 is much less abundant than Akt2 in adipocytes (7, 27, 28). In contrast, reduction of Akt2 expression by ≈70% caused a marked 55–60% decrease in insulin-stimulated Thr phosphorylation of the Akt protein kinases (Fig. 3). Taken together, these data confirm the predominance of Akt2 over Akt1 in insulin-sensitive cultured adipocytes (7).
Next, we assessed the consequences of the selective attenuation of Akt1 or Akt2 expression on a downstream target of insulin signaling–GSK-3 (29, 30). GSK-3α is phosphorylated by Akt protein kinases in response to the hormone in a dose-dependent manner (Fig. 4). In three independent experiments, loss of 95% or more of Akt1 directed by the akt1b siRNA caused no significant attenuation of insulin-mediated GSK-3α phosphorylation (Fig. 4 A and B), although a 10–20% effect may go undetected in these studies. In contrast, attenuation of Akt2 expression by 70% caused ≈40% inhibition of insulin-mediated GSK-3α phosphorylation (Figs. 4 A and B and 5 A and C). In control studies, no diminution of insulin signaling to the mitogen-activated protein kinases Erk-1 and Erk-2 was observed when either Akt1 or Akt2 are depleted (Fig. 4 C and D), confirming the specificity of the effect of silencing the Akt protein kinases by this method. These data indicate that insulin action on GSK-3α in cultured adipocytes specifically requires Akt2.
Redundancy of Akt1 and Akt2 in Insulin Signaling. Applying this same approach to hexose transport regulation, we found that ablation of Akt1 expression (Fig. 5A) leads to a small but significant 20–30% decrease in insulin-stimulated 2-deoxyglucose uptake in 3T3-L1 adipocytes (Fig. 5B). Akt2 protein depletion to ≈70% of normal levels dampened the insulin response by 50–58%. These data indicate that both Akt1 and Akt2 contribute to insulin responsiveness of hexose transport in cultured adipocytes roughly in proportion to their contributions to total activated Akt in these cells (see ref. 7 and Fig. 3). We then tested the effects of depleting both Akt1 and Akt2 in 3T3-L1 adipocytes by using the combination of akt1b and akt2b siRNA species (Fig. 5 A and C). This combined treatment virtually completely ablated Akt1 expression and reduced Akt2 expression by >65% whereas insulin-stimulated phosphorylation of total Akt detected by anti-phospho Thr-308/309 Ab decreased by 81% (Fig. 5A). Importantly, insulin-stimulated deoxyglucose uptake was inhibited by nearly 80% under these conditions, compared to ≈58% when only Akt2 was depleted (Fig. 5C). Under these conditions, GLUT4 expression was unchanged (not shown). In control experiments to test whether engagement of the gene silencing process itself nonspecifically inhibits insulin signaling, we observed no significant effect of lamin siRNA on insulin-stimulated glucose transport under conditions where lamin A/C protein levels were markedly reduced (Fig. 1 and data not shown). Taken together, these data demonstrate that although Akt2 is the major protein kinase required in this response, Akt1 can also play a role. Thus under conditions where insulin-stimulated glucose uptake is significantly compromised by partial depletion of Akt2, Akt1 is required for half of the remaining insulin signal (Fig. 5C). GSK-3α phosphorylation in response to insulin was also inhibited to a greater extent when both protein kinases were depleted vs. when only Akt2 was reduced (Fig. 5 A and C).
In additional control experiments, we tested whether expression of other insulin-signaling elements such as IRS proteins (31, 32) or PKCλ/ζ (11, 33) is affected by Akt1 or Akt2 siRNAs. As shown in Fig. 5A, depletion of Akt1 or Akt2 had no significant effect on insulin-stimulated tyrosine phosphorylation of IRS proteins or expression levels of PKCλ/ζ.
The effect of combined depletion of both Akt1 and Akt2 by siRNA on insulin-mediated GLUT4 translocation was next examined in 3T3-L1 adipocytes. Cotransfection of myc-GLUT4-EGFP plasmid DNA with the mixture of akt1b and akt2b siRNAs was performed, and 48 h later reductions of ≈90% and 65% of Akt1 and Akt2 protein levels, respectively, were observed (Fig. 6B). This combined knockdown of Akt1 and Akt2 proteins resulted in the loss of insulin-stimulated cell surface Myc signal (detected by anti-Myc Ab) in ≈70% of adipocytes transfected with the Myc-GLUT4-GFP construct (Fig. 6 A and C). Quantifying the ratio of cell surface Myc rim signal over the total Myc-GLUT4-GFP signal in positive transfected cells revealed that loss of both Akt1 and Akt2 resulted in a 60% decrease in insulin-stimulated Myc-GLUT4-GFP on the cell surface (Fig. 6D). The attenuation of GLUT4 responsiveness is observed at both maximal and submaximal concentrations of insulin (Fig. 6C), whereas no significant effect of Akt depletion on GLUT4 translocation in the absence of insulin is detected.
The findings presented here show an absolute requirement of Akt protein kinases for normal insulin signaling to glucose transport and GSK-3α and imply direct proportionality of total available Akt1 plus Akt2 to the degree of insulin responsiveness (Fig. 5). This conclusion is in keeping with the similar insulin dose–response relationships observed for activation of total Akt and glucose transport (compare Figs. 3C and 5B). Progressive loss of Akt1, Akt2, or both leads to a correspondingly progressive loss in glucose transport stimulation (Fig. 5). These considerations show that Akt1 can in part replace Akt2 to sustain glucose transport responsiveness, potentially providing an explanation for why skeletal muscle of Akt2–/– mice exhibits only a mild impairment in insulin responsiveness (10). No data on insulin signaling in muscle or fat cells from Akt1–/– mice have been published, but the normal glucose tolerance in these animals (12) is consistent with our data (Fig. 5) that Akt2 alone can sustain most of the insulin-regulated glucose uptake. Although it is possible that other signaling pathways (22, 34, 35) and protein kinases are also involved in insulin action on glucose transport, our results underscore the absolute requirement of Akt for this process.
We thank Dr. Morris J. Birnbaum for kindly providing anti-Akt2 Ab and Jane Erickson for assistance with the manuscript. This work was supported by National Institutes of Health Grants DK30648 and DK60837 (to M.P.C.).
↵§ To whom correspondence should be addressed. E-mail: michael.czech{at}umassmed.edu.
↵† Z.Y.J. and Q.L.Z. contributed equally to this work.
Abbreviations: GLUT4, glucose transporter 4; GSK-3, glycogen synthase kinase-3; siRNA, small interfering RNA; Acrp30, adipocyte complement-related protein of 30 kDa; IRS, insulin receptor substrate.
- Received December 24, 2002.
- Copyright © 2003, The National Academy of Sciences
- ↵
- ↵
Cushman, S. W. & Wardzala, L. J. (1980) J. Biol. Chem. 255, 4758–4762.pmid:6989818
- ↵
- ↵
White, M. F. (2002) Am. J. Physiol. 283, E413–E422.
- ↵
Czech, M. P. & Corvera, S. (1999) J. Biol. Chem. 274, 1865–1868.pmid:9890935
- ↵
Kohn, A. D., Summers, S. A., Birnbaum, M. P. & Roth, R. A. (1996) J. Biol. Chem. 49, 31372–31378.
- ↵
Hill, M. M., Clark, S. F., Tucker, D. F., Birnbaum, M. J., James, D. E. & Macaulay, S. L. (1999) Mol. Cell. Biol. 19, 7771–7781.pmid:10523666
Wang, Q., Somwar, R., Bilan, P. J., Liu, Z., Jin, J., Woodgett, J. R. & Klip, A. (1999) Mol. Cell. Biol. 19, 4008–4018.pmid:10330141
Ueki, K., Yamamoto-Honda, R., Kaburagi, Y., Yamauchi, T., Tobe, K., Burgering, B. M., Coffer, P. J., Komuro, I., Akanuma, Y., Yazaki, Y., et al. (1998) J. Biol. Chem. 273, 5315–5322.pmid:9478990
- ↵
Cho, H., Mu, J., Kim, J. K., Thorvaldsen, J. L., Chu, Q., Chrenshaw, E. B., Kaestner, K. H., Bartolomei, M. S., Shulman, G. I. & Birnbaum, M. J. (2001) Science 292, 1728–1731.pmid:11387480
- ↵
Kotani, K., Ogawa, W., Matsumoto, M., Kitamura, T., Sakaue, H., Hino, Y., Miyake, K., Sano, W., Akimoto, K., Ohno, S. & Kasuga, M. (1998) Mol. Cell. Biol. 18, 6971–6982.pmid:9819385
- ↵
Cho, H., Thorvaldsen, J. L., Chu, Q., Feng, F. & Birnbaum, M. J. (2001) J. Biol. Chem. 276, 38349–38352.pmid:11533044
- ↵
- ↵
- ↵
- ↵
Hammond, S. M., Bermstein, E., Beach, D. & Hannon, G. J. (2001) Nature 404, 293–296.
- ↵
Hammond, S., Boettcher, S., Caudy, A., Kobayashi, R. & Hannon, G. J. (2001) Science 293, 1146–1150.pmid:11498593
- ↵
- ↵
Elbashir, S. M., Lendeckel, W. & Tuschl, T. (2000) Genes Dev. 15, 188–200.
- ↵
- ↵
Jiang, Z. Y., Chawla, A., Bose, A., Way, M. & Czezh, M. P. (2002) J. Biol. Chem. 277, 509–515.pmid:11694514
- ↵
Harrison, S. A., Buxton, J. M., Clancy, B. M. & Czech, M. P. (1990) J. Biol. Chem. 265, 20106–20116.pmid:2173694
- ↵
- ↵
- ↵
Summers, S. A., Whiteman, E. L., Cho, H., Lipfert, L. & Birnbaum, M. J. (1999) J. Biol. Chem. 274, 23858–23867.pmid:10446150
- ↵
Calera, M. R., Martinez, C., Liu, H., El Jack, A. K., Birnbaum, M. J. & Pilch, P. F. (1998) J. Biol. Chem. 273, 7201–7204.pmid:9516411
- ↵
- ↵
- ↵
Li, J., DeFea, K. & Roth, R. A. (1999) J. Biol. Chem. 274, 9351–9356.pmid:10092613
- ↵
Paz, K., Liu, Y.-F., Shorer, H., Hemi, R., LeRoith, D., Quan, M., Kannah, K., Seger, R. & Zick, Y. (1999) J. Biol. Chem. 274, 28816–28822.pmid:10497255
- ↵
Standaert, M. L., Galloway, L., Karnam, P., Bandyopadhyay, G., Moscat, J. & Farese, R. V. (1997) J. Biol. Chem. 272, 30075–30082.pmid:9374484
- ↵
- ↵
Wang, Q., Bilan, P. J., Tsakiridis, T., Hinek, A. & Klip, A. (1998) Biochem. J. 331, 917–928.pmid:9560323


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The Future
The future of facilities, installations and campuses—collectively installations—is to become a smart installation. There's no way for you to avoid making your installation smart. With fewer resources and additional forces such as external threats, mandates, laws and the fidelity of information required to boost your key performance indicators (KPIs), you must do something.
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Esri partners, such as GISincorporated, are your go to solution providers for affordable solutions that can be quickly implemented. GISInc offers an initial operating capability for asset management.
Using both indoor and outdoor tracking technologies (GPS, WiFI, BlueTooth, VLC, RFID) we are able to track movement and status of critical assets in a spatial context. This allows Facilities Managers and Operation Managers to reduce loss and theft, find critical assets when needed, and monitor and document workflow processes associated with those assets.
Empowering your workforce and digitally transforming any single aspect of your asset management system aids individual workers and provides a common map and dashboard view to see the status of projects. Installations can start with a smart lighting system with high efficiency fixtures and automated controls to make adjustment based on conditions such as occupancy or daylight availability. Such projects allow the community to create a workflow model that, with minor configuration, can be replicated across your enterprise.
Learn more, watch and participate in the Smart Installations webinars.
Read more Smart Installations: Facilities Management and Sustainability


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Disclaimer: The following is post a compilation of some mad ideas that cropped up in my head after a very heavy dinner from Park Rajadhani. Any resemblance to any women living or dead is entirely coincidental and a fabric of the reader's imagination, even if it somehow became true!
What was God thinking when he made women? May be he thought, men needed to have an ultimate question for which when the answer is found, the question simply changed!
Some snippets I have observed over a long period of time. Nothing personal, some general observations. The 'She' does not in anyway encompass the entire female race!
She: He is too cute. I don't like cute guys.
She: If only he was cute...
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I don't think I quite pulled this one off :-D
1 day ago


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"For most, homelessness is the result of a lack of supports, mental health issues and addiction." — Calgary Dream Centre Calgary Dream Centre's invaluable mission is to guide men and women caught in cycles of poverty and addiction into lives of purpose. The Centre first opened its doors in 2004 and has been helping homeless…
Langley Memorial Hospital Foundation & Northwest
"Because of the Foundation's donation, we have equipment that would have been difficult to afford through regular funding. It's so important that we have the state-of-the-art technology and equipment so I can offer the absolute best care to every patient. Donors make that possible." — Dr. Carolyn Anderson, Ophthalmologist at Langley Memorial Hospital The Langley Memorial…
Big Brothers Big Sisters & Northwest
"Think of someone who has inspired you. Do they make you feel confident, smart, brave? Now, imagine your life without them. Where would you be today?" Big Brothers Big Sisters of Canada envisions a world where everyone has that person. They are committed to enhancing the confidence, self-esteem and well-being of children through invaluable mentor…
Northwest Partners with the Canadian Cancer Society
At Northwest, we are all about supporting the communities in which we live and work. One of the ways we do this is through partnerships with philanthropic organizations and initiatives. This year marked the beginning of one such partnership with the Canadian Cancer Society.
What's better than the Good Housekeeping Seal of Approval? If you're a company involved in the chemical industry, it could be Responsible Care-In-Place Verification, a way to help ensure safety and efficiency in handling what could be extremely dangerous substances.


text: I know it's possible in Java to build a DOM tree out of a SAX ContentHandler and store the line/column number into the DOM3 UserData field. Has anyone actually packaged this up as an open source library anywhere? All I find on the Web are examples of doing this, no finished products. -- Elliotte Rusty Harold firstname.lastname@example.com


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Unity game development
I'm getting into things again. And this time it may end up being something productive!
So yeah, I went and tried out Unity. For those of you not aware, it's an engine for making games. Messed around with it a bit before giving up on trial and error, and grabbed myself a good tutorial or two. Started out with a not all that great one, but it taught me the very basic basics, as well as some scripting in JavaScript. I shouldn't call it that though, it's more like UnityScript. Anyway, I'd much rather use C# (the more strict language (and strict is better for learning, trust me), and the tutorial's pacing was a bit bad, so I searched for another one.
And then I stumbled upon this gem. It's a very well-written tutorial. It explains everything pretty well, the pacing is great, it provides you with good code, and features some solid know-how that can easily be applied to other projects. Granted, he didn't mention the importance of typing the code yourself instead of copy-pasting it, but hey, people should be smart enough to know that, right?
I finished it today, and have created a very simple 2D platformer, with a 3D graphical touch. Granted, it's all cubes, but it works, and it's great. That feeling of proudness has returned, the one you get when learning a new skill and making something that seems real simple, but still has some complicated underlying mechanics. I'd publish it to the internet (yes, that is a thing I can do. Yes, you'd be able to play it,) but I'm not quite satisfied with it yet. It's kind of boring, luck-based, and the graphics could do with a bit of a boost. Besides, it's still not much different from the tutorial, so I'd like to give my own twist to it first. After that, who knows, you may get to play it.
Off to bed now, 'twas a tiring day.
~ Fang


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From The Collaborative International Dictionary of English v.0.48 [gcide]:
Breach \Breach\ (br[=e]ch), noun [OE. breke, breche, AS. brice, gebrice, gebrece (in comp.), fr. brecan to break; akin to Dan. br[ae]k, MHG. breche, gap, breach. See {Break}, and cf. {Brake} (the instrument), {Brack} a break] .
1. The act of breaking, in a figurative sense.
2. Specifically: A breaking or infraction of a law, or of any obligation or tie; violation; non-fulfillment; as, a breach of contract; a breach of promise.
3. A gap or opening made made by breaking or battering, as in a wall or fortification; the space between the parts of a solid body rent by violence; a break; a rupture.
Once more unto the breach, dear friends, once more; Or close the wall up with our English dead. --Shak.
4. A breaking of waters, as over a vessel; the waters themselves; surge; surf.
The Lord hath broken forth upon mine enemies before me, as the breach of waters. --2 Sam. v. 20.
{A clear breach} implies that the waves roll over the vessel without breaking.
{A clean breach} implies that everything on deck is swept away. --Ham. Nav. Encyc.
5. A breaking up of amicable relations; rupture.
There's fallen between him and my lord An unkind breach. --Shak.
Breach for breach, eye for eye. --Lev. xxiv. 20.
7. (Med.) A hernia; a rupture.
8. A breaking out upon; an assault.
The Lord had made a breach upon Uzza. --1. Chron. xiii. 11.
{Breach of falth}, a breaking, or a failure to keep, an expressed or implied promise; a betrayal of confidence or trust.
{Breach of peace}, disorderly conduct, disturbing the public peace.
{Breach of privilege}, an act or default in violation of the privilege or either house of Parliament, of Congress, or of a State legislature, as, for instance, by false swearing before a committee. --Mozley. Abbott.
{Breach of promise}, violation of one's plighted word, esp. of a promise to marry.
{Breach of trust}, violation of one's duty or faith in a matter entrusted to one.
Syn: Rent; cleft; chasm; rift; aperture; gap; break; disruption; fracture; rupture; infraction; infringement; violation; quarrel; dispute; contention; difference; misunderstanding.
Definitions retrieved from the Open Source DICT Webster's English and WordNet 3.0 dictionaries. Click here for database copyright information.
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When my son got injured I desperately needed advise but had no idea who to call. Someone highly recommended I contact Greg Monforton and Partners, so I did. I didn't think that anyone would truly care or be interested in what I was going through but Brad Robitaille and Rachael Bondy definitely were. They demonstrated genuine concern for my son's health, safety, and wellbeing, and provided me with guidance, advice, and support. They truly stood by the core values listed on the firm's website that governs the actions of everyone in their firm: RESPECT FOR THE INDIVIDUAL MAJOR ATTENTION TO SERVICE SUPERIORITY IN ALL THINGS I am truly thankful for the support they have provided and continue to provide. I don't feel as scared and alone dealing with my son's injury. I feel supported and can now focus all my attention on my son's recovery and reintegration into school and community. Thank you. Catherine Dobry
Even though we haven't opted to proceed with my potential case, I was very satisfied with the way Sarah followed up with me regularly. She always checked in with me when she said she would, in order to check on the status of my injuries. I was very impressed with the thorough notes she kept, as well as with the follow-up questions she would have any time we spoke. I'd highly recommend Greg Monforton and Partners to anyone looking for legal representation after an accident. John Stearns
Thank you Kindly for timely and very helpful reply. Andre Martin
They returned my call the next day and answered all of my questions. Very knowledgeable. Freddy
Absolutely recommend! They recently helped me with a long term disability case and were spot on! Would certainly recommend no questions asked. John Adams
On the first consultation I received answers to my questions and advice regarding my options. The phone call was very helpful in planning how to proceed. Meg Meg Connelly
Called and got advice on my brothers case. Information was very helpful. Sarah Halabi
Answered all my questions before I even asked. Very satisfied. Linda Lalonde
Received a call back within a couple hours. Sarah was very friendly and helpful. Took the time to review our situation and answer all of our questions, making a difficult time easier. Brandon Bezaire
Great service Donna Moise
I applied for a free evaluation and within a couple hours i was contacted ,helped and reassured definitely the best experience with a law firm i have had. Thank you Lieven Girard
Very easy to talk with, understanding and thorough. Very helpful giving advice on what direction to take. Susan Ferriss
Excellent Law Firm!! Very Helpful, knowledgeable, quick responses & great results!! Would definitely recommend Greg Monforton his Partners & associates!!👍👍 Kathy Nicholson
Very kind, patient and willing to assist with dealing with what can feel like an overwhelming life experience. Thanks Sarah. Carrie Adams
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You were all absolutely wonderful and amazing. Thanks so very much for all your support, hints, patience, and expertise. Sincerely, Linda van Omme Linda Van Omme
Answered all questions. Lots of good information. Josh Epp
Thank you for your kindness, compassion, and willingness to listen and help us every step of the way. It was truly appreciated. Tara Louise
I have contacted this law firm on numerous occasions over the past 30 years for legal advice on various issues. I have always been treated with the utmost of courtesy and professionalism in my dealings with the entire legal team at Greg Monforton and Partners. I have found the Monforton family of lawyers to be caring, knowledgeable and sensitive to my inquires at all times. They have gone above and beyond to provide exemplary service. It is without hesitation that I recommend Greg Monforton and Partners as the law firm of choice. Karen May
An excellent Law Firm to visit The staff is very pleasant and the lawyers attribute 100% plus to your situation. Highly recommended Darcy Bayliss
For over 15 years I have worked as an Occupational Therapist treating individuals who have sustained serious injuries as a result of MVAs. During my time as an OT many of my clients have been represented by the team at Greg Monforton and Partners. The firm's knowledge of the law is unparalleled, as is their determination to ensure that all individuals represented are fairly rewarded and compensated for their loss of life roles and enjoyment of life resultant of the accident. As an OT it was great to work with a team that understands the need and importance of therapy/ rehabilitation for healing; they focus on ensuring their clients have the funding required for treatment programming necessary to maximize recovery and quality of life after a trauma, both today and into the future. I have seen first-hand an unmatched level of respect, compassion and caring for the injured individuals, and their families. Laura Thompson Wilkie


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Business Leader and Philanthropist Robert Shumake Drills a Water Well in Rural Kenya
That's why business leader, entrepreneur, bestselling author, and international philanthropist Robert Shumake of Detroit, Michigan, is using his nonprofit charity's funds to drill a watering hole in a rural area of Kenya. Water projects in Kenya are notoriously underfunded, and the equipment and labor are often too costly for locals to provide. The Robert Shumake Family and Friends Foundation will complete the project in early 2020, providing funds, labor, and equipment. The nonprofit has hired experts to ensure the project's ongoing success in terms of sustainability and infrastructure.
The 10,000-liter water well is estimated to provide hydration for over 1,000 villagers near the area, as well as 300 schoolchildren and a large number of animals. The water quality will be tested by qualified technicians. In total, the project is expected to take around a week of labor by approximately a dozen employees and volunteers.
"The difficulty of finding clean drinking water in Kenya is a challenge to individual wellness and public health," says Robert Shumake. "Children and infants may go days without water, which poses particular health problems for them, as well as for pregnant women and elderly citizens. We at the Robert Shumake Family and Friends Foundation wanted to help solve to solve this major problem as soon as we learned about it. We matched individual donations and will provide all the necessary time, labor, and equipment to complete the task. Our hope is that the project will greatly improve villagers' and students' health, happiness, and quality of life. If successful, we will helm similar projects in the future."
Robert Shumake leads the L3C enterprise Shumake Global Partners, which deals with infrastructural projects, real estate, technology, education, and healthcare. Through the Robert Shumake Family and Friends Foundation, Robert Shumake has a long history of contributing to international projects, such as launching the Shumake Legacy Academy for HIV-positive orphans in Ethiopia. He also contributes to local projects, such as the Robert Shumake Scholarship Relays, which provides educational funding for college students headed to historically black colleges and universities (HBCUs).
Caroline Hunter
Web Presence, LLC
+1 7862338220
email us here
EIN Presswire does not exercise editorial control over third-party content provided, uploaded, published, or distributed by users of EIN Presswire. We are a distributor, not a publisher, of 3rd party content. Such content may contain the views, opinions, statements, offers, and other material of the respective users, suppliers, participants, or authors.


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Concise Elegant Red Tote Handbag with Lizard Pattern
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- Item NO.:MBNO039027
- Material:Outer:PU leather, Lining:Fabric
- Function:For daily
- Exterior:Lizard pattern
- Interior:1 zip pocket and 2 slip pockets
- Size:14"L x 5.5"W x 11.5"H
A new design for sophisticates on the go. This Lizard Pattern Red Tote Handbag is a best choice for women who appreciate luxury but also love the on-trend elegant style.
Completing with rigid double handles, the well-organized interior accommodates a full day's worth of daytime essentials.
Price: $50.00 / Piece
Sample Policy:
- Refund:Once you place an order of MOQ≥200/style/color, we will refund the sample fee to you.
- Payment Method: PayPal
- Sample-making Required Time: 7 business days.
- Design:Logo, color, hardware, etc. can be customized.
- Sample Shipping:Please note that the shipping fee is not included in the sample fee mentioned above. And if you want to calculate the shipping fee and the approximate shipping required time, please check on the "SHIPPING" tab.
- Package Packing:1 pc/non-woven bag and 1 opp bag.
- Purchase Invoice: We can offer you the purchase invoice, please contact our staff.
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|14.00in x 5.50in x 11.50in
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Your Play AU journey starts here. Depending on your ability level and sport we can provide a stack of great perks as part of any player or coach package we secure for you. This can include things like payment for playing, accommodation assistance, waived club membership fees, well-paid coaching contracts, officiating work and a host of other benefits to help you settle into Aussie life and live like a local.
Before we can get you hooked up with sporting opportunities down-under we need to firstly verify your eligibility so we can ensure you have what it takes to join our program.