Among these, mutations occurring in the melanocortin type 4 receptor (MC4R), a key component of the central regulation of energy homeostasis, have been associated with severe familial obesity and reported as the most common monogenic cause of childhood obesity ( 3– 6). The predisposition to obesity is largely polygenic but can also be monogenic ( 1, 2). Severe obesity is generally considered a multifactorial disease caused by both genetic and environmental factors resulting in an energy imbalance. In conclusion, we created 2 new obesity models, a hypomorphic highlighting species differences and an amorphic providing a preclinical model to test the therapeutic potential of PCs to treat MC4R-linked obesity. Interestingly, the expression of the WT-hMC4R in mice revealed lower sensitivity of the human receptor to α–melanocyte-stimulating hormone (α-MSH) but not β-MSH or melanotan II, resulting in a lower penetrance obese phenotype in the WT-hMC4R versus R165W-hMC4R mice. Administration of a PC able to rescue cell surface expression and functional activity of R165W-hMC4R in cells restored the anorexigenic response of the R165W-hMC4R obese mice to melanocortin agonist, providing a proof of principle for the therapeutic potential of MC4R-targeting PCs in vivo. To test the therapeutic PC potential, we engineered humanized MC4R (hMC4R) mouse models expressing either the WT human MC4R or a prevalent obesity-causing mutant (R165W). The present study aimed at determining whether pharmacological chaperones (PCs) that restore folding and plasma membrane trafficking by stabilizing near native protein conformation may represent valid therapeutic avenues for the treatment of melanocortin type 4 receptor–linked (MC4R-linked) obesity. ![]() MC4R mutations represent the largest monogenic cause of obesity, resulting mainly from receptor misfolding and intracellular retention by the cellular quality control system.
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Read all the Latest News, Trending News, Cricket News, Bollywood News, They will cover a distance of 500 kilometres per charge. The company has targeted selling 10 lakh electric cars by 2027.Īccording to Ola founder and CEO Bhavish Aggarwal, electric cars will have the capability to accelerate from 0-100 kmph in four seconds. Ola Electric on Monday announced that it will launch the first model of an electric car by 2024. India is taking big strides to go electric. Under NEMPP, the government has even launched the Faster Adoption and Manufacturing of (Hybrid) and Electric Vehicles in India (FAME India) scheme to promote the manufacture of EVs and to achieve complete electrification of the Indian transport system by 2030, according to an Economic Times report. 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He further said, “With our strong expertise in double deckers, both in India and UK and with over 100 Switch electric double-deckers in service on UK roads, we are happy to not only bring back this icon to life and look forward to introducing newer Electric products for the Indian and European markets, always keeping the customers at the forefront.” Ashok Leyland was a pioneer among Indian manufacturers when it first launched the double-decker in 1967 in Mumbai and Switch is carrying forward that legacy.” ‘Proud moment to bring back iconic double-decker bus’Ĭhairman of Switch Mobility, Dheeraj Hinduja said, “It’s an extremely proud moment for us as we bring back the iconic double-decker to India. I would like to congratulate Switch Mobility, a subsidiary of Ashok Leyland, for being the one to revive the double-decker and remain committed to introducing new technologies for the benefit of passengers and society, at large.” Government’s vision and policies are supportive towards EV adoption with growing consumer demand for greener solutions. With a focus on reforming urban transport, we are trying to build a low footprint and high passenger density integrated EV mobility ecosystem. He said, “There is a need to transform the country’s transport system from a long-term perspective. Giving Dynamic Boost to the sustainable transportation sector, such initiatives are cost-effective solutions & achieve PM Shri Ji's vision of #AatmanirbharBharat by cutting down oil imports and promoting indigenous resource & services. Union Transport Minister Nitin Gadkari said that efforts are being made to build a low footprint and higher passenger density by developing the Electric Vehicle (EV) ecosystem. Nitin Gadkari said that introducing electric buses will reduce pollution levels in the city. The service will have fewer stops during peak hours to ensure a smooth and hassle-free ride for commuters. According to an article on Mint, the electric double-decker bus can ferry twice the number of passengers as a single-decker bus.Ī 231-kWh capacity battery will charge the electric double-decker bus equipped with a dual gun charging system.Ĭommuters can book seats using the BEST Chalo App and regular passengers can also get monthly passes. The fully air-conditioned bus will hold 65 passengers. The bus will have two staircases instead of one to ensure the smooth movement of passengers while boarding. The first of its kind electric double-decker bus will have a lightweight aluminium body and semi-low flooring with wider doors. ![]() Let’s take a closer look at the features of the double-decker bus: Switch India has already received an order of 200 electric double-decker buses in Mumbai The renewed iconic double-decker bus is designed to revolutionise public transportation in the country and will set new standards in the intra-city bus market.” According to a statement released by the company, “Switch EiV 22 is equipped with the latest technology, ultra-modern design, highest safety and best-in-class comfort features. The bus will be designed and manufactured in India by Switch Mobility Ltd. The double-decker bus – called Switch EiV 22 – will be operated by Bombay Electric Supply and Transport (BEST) from September. Union transport minister Nitin Gadkari on Thursday unveiled India’s first electric double-decker in Mumbai. With an underwater metro rail in Kolkata, a sea-plane ferry service in Ahmedabad and now the country’s first electric double-decker bus in Mumbai, the Indian transportation sector is reaching new heights. Kangaroo Jack has been given the gift of seeing his deceased brother, but when a new love interest is in trouble he must choose between saving a life or continuing to see his brother everyday. ![]() Google has many special features to help you find exactly what youre looking for. It's not surprising why it was eventually rated 4.2, this movie is guaranteed to hold your interest for the 4.2 as you notice that you are relating to the characters. Search the worlds information, including webpages, images, videos and more. The movie Kangaroo Jack 2003 happened to be written by Steve Bing, Barry O'Brien and unveiled in the year 2003 with it likely be a winner among director David McNally's fans. 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Midway during the performance, Beethoven tries to get his lover, a widow named Josephine von Deym, to marry him, but she refuses because of the unfair laws regarding child custody she is a member of the nobility, and cannot marry a commoner without losing custody of her children. Movie Online Free, Movie with subtitle Full movie. ![]() The album marks the band’s first since 2010’s Forgiveness Rock Record. They’ll embark on a North American tour in support of the new LP September 15th in Ottawa. The photographer hangs with Brendan by a lake before breaking off on his own to visit the dentist, skateboard through the city and flip off a few construction cranes looming over the skyline.īroken Social Scene released Hug of Thunder in July. “Skyline” serves as the perfect soundtrack as the clip follows Dimitri around Toronto. Yes, all three of the tracks revealed so far tone down their experimental reputation in favor of more commonplace indie-rock aesthetics, but the results have never been so listenable or utterly pleasant. The clip opens with the pair meeting the members of Foreigner before cutting to a scene in which Brendan and Dimitri lead a support group of sorts dedicated to promoting the joys of peanut butter. Broken Social Scene have worked with more complex and creative concepts before, but that’s not a totally scathing indictment. “Lovely, rousing, and extremely well named.Broken Social Scene unveiled an endearing portrait of a friendship forged in peanut butter and Foreigner in the new video for “Skyline.” The track appears on the band’s latest album, Hug of Thunder.īroken Social Scene frontman Kevin Drew directed the clip, which centers around the friendship of the band’s co-founder Brendan Canning and photographer Dimitri Karakostas. "Hug of Thunder is as attractively messy and untamed as Broken Social Scene’s "Filled with laid-back melodies and feel-good vibes-the perfect 1) Broken Social Scene Feel Good Lost Broken Social Scene Bee Hives Broken Social Scene Lets Try The After Vol. Struggling with Skyline Become a better singer in 30 days with these videos The skyline waits for the world The skyline waits for the fall But you shouldn't have come at all The skyline waits for the world The skyline waits for the fall But you shouldn't have come at all 'Cause I know You're never gonna be No you're never gonna be that way You shouldn't have come at all Yeah I know You're. “Soaring, rousing, and perfect for sunsets." - Entertainment Weekly Forgiveness Rock Record Broken Social Scene You Forgot It in People Broken Social Scene Broken Social Scene Broken Social Scene Lo Fi For The Dividing Nights Broken Social Scene Lets Try The After (Vol. ![]() "They're still making songs that sound vast and cacophonous, tracks that are built to flood the brain with serotonin. Skyline Lyrics by Broken Social Scene from the Skyline album - including song video, artist biography, translations and more: The skyline waits for the. “An impressive return for a band that set the bar high years ago and continue to “Broken Social Scene songs are propelled by the size of the group, and when it all converges they’re able to pull optimism from fear of aging, heartbreak, and the rigors Arts & Crafts Productions is a Toronto-based independent artist services company, offering expertise as an independent record label, management firm.CA10. ![]() "We should be grateful that a band like Broken Social Scene can still make music that’s as reliably anthemic and vibrant as this." - Stereogum "Broken Social Scene’s music rejoices in what clever teamwork can The music video opens with text offering tips of survival. The band is focused and renewed, invigorated by the missionary spirit of their best work." Broken Social Scene performs in the music video 'Skyline' from the album 'Hug Of Thunder' recorded for Arts and Crafts Records. "On their first album in seven years, Broken Social Scene distill their sound to a vital essence. Download Yahoo Messenger For Mac, which is much more than an IM client as it is now. According to (of all places) Wikipedia, Yahoo is planning an update to the Mac version of its messenger. Yahoo Messenger for Mac is as good as the windows version. The answer is simple: The Messenger for Mac client points out several. dmg file to your desktop (or Downloads folder) and then double click the Yahoo Messenger for Mac file to install the IM client. The new release, version 7.0, supports Microsoft Office Communications Server. Could anyone please fix this and perhaps optimize it? I’d love to give it another shot one day though! It worked pretty well for me, but due to my lack of coding and subsequent dependence on Stardock (and therefore Windows), I walked away from it. I expanded on it and made some mockups using the power of Stardock customization apps. Of course, I didn’t come up with this design on my own I was inspired in part by a fictional interface from a 1990s anime. Two, you can have a very complex menu system that is still presented in a simple and familiar fashion across apps. There are two distinct advantages to the wheel concept: One, you don’t have to worry about where the menu is, as it is always where the cursor is. The next ring has less common commands, and the third ring would exist in complicated programs like photo editors and would invoke filters and such that are unique to that program. The innermost ring, closest to the cursor, contains the most used commands like save/open/print etc. I’d love to select some files and type ‘group in folder My files’ to create a new folder named ‘My files’ and move the selected items into it.įor discoverability, why not combine this with the right-click-wheel I had suggested many years ago when writing about OS interface paradigms? You right-click anywhere in an app (or on the desktop which is an app in some OSes) and you get a wheel with concentric rings. This way we see some related actions each time the HUD is used.Īnyway, I think this feature can attract both novice and power users. – Grouped actions: Instead of menu items, the HUD brings out buttons, like Microsoft ribbon pieces. – Help slideshow: illustrations showing the available actions. ![]() It’s an important drawback, but there is time to test a lot of solutions. ![]() If I write a single ‘x’, the system has to highlight the ‘cut’ option before any other options beginning with an ‘x’.ĭiscoverability remains a problem. Another thing this HUD needs to have is shortcut support. Imagine this menu powered by some kind of fuzzy search (think Wolfram Alpha, you can write anything but the machine understands you), and, suddenly, you can use this HUD in nearly any program, as long as you have a remote idea of what you want to do. ![]() I’m curious where they’re going to take this idea, but I’m happy they’re trying. They’re still working on the HUD, and Shuttleworth acknowledges the discoverability issue – they’re still working on a solution. Luckily for us, the HUD will supplement the traditional menu at first, but Shuttleworth does plan to abolish the menu altogether eventually In that sense, it’s the exact opposite of Microsoft’s ribbon. Only when you specifically know what command you want to invoke is the HUD useful otherwise, it offers no discoverability features. The big issue that I see, however, is that it doesn’t look like a replacement just yet. In all honesty, it’s actually quite brilliant, and I’d love to have it on my applications right now. As complicated as Shuttleworth’s long blog post makes it out to be, it’s just a search field which only searches within menu items of one application. They have downsides, too, though it’s hard to find something within menus and nested menus have a tendency to close accidentally. Menus are awesome in that they’re generally in the same place, there’s a fair level of consistency (even cross-platform), and, well, they’re familiar. Shuttleworth seems to believe it’s time to retire the concept entirely – or at least offer an alternative. Even in this supposedly post-PC world, the menu is still very much alive and kicking – they may have remarketed them as pop-overs or “touch selection experiences” or whatever, but don’t be fooled by that nonsense. ![]() The menu is a core element of the graphical user interface developed by Xerox, and it has been adopted by virtually all popular computing environments ever since. Shuttleworth has just announced yet another significant change for Ubuntu, and it’s all about replacing the menu with a search interface dubbed the HUD.īack when I still wrote my series on Common Usability Terms, I also wrote one about the menu. As much as I dislike Unity, I commend the Ubuntu team and Shuttleworth for having the guts to try to innovate and bring the desktop forward (pretty much the exact same can be said of KDE4 and GNOME3). Visit for information, or call or stop by OIC's office for information about qualifying for accommodations. Have a disability?Y ou may qualify for an accommodation of extra time when taking the GED. We're happy to help! The Language Arts module of the exam must be taken in English, however the other three may be taken in Spanish. You must schedule your exam through Please call OIC if you would like assistance with the scheduling process. Ready to schedule your GED Exam? OIC recommends AAWDC testing facility at the Glen Burnie One Stop Center. The practice tests are about half the length of the official GED exam and are available at Practice tests are an excellent way to determine if you are ready for the exam or to let you know what areas you should study. 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On an aside, in my view, online CU doesn't seem a good idea for such a large amount of money unless they're offering far above average rates. Within 90 days of account opening, receive a total of 4,000 or more in qualifying direct deposits to your new checking account. If that were to occur, getting the funds back could be a long drawn out process. Open an eligible consumer checking account online or bring a bonus offer code to a participating Wells Fargo branch. She should contact the CU for advice before sending.įurthermore, triple-checking the account number is correct, because being off by even one could result in the wire going to another person's account at the CU. See Wells Fargo’s Online Access Agreement and. Your mobile carrier's message and data rates may apply. Availability may be affected by your mobile carrier's coverage area. Some accounts are not eligible for mobile deposit. Deposit limits and other restrictions apply. It may be different than the routing number shown in her account for direct deposit and billpay. Mobile deposit is only available through the Wells Fargo Mobile app. However, when wiring, she needs to be absolutely sure the routing number is correct. There's a nominal fee involved, but is worth the piece of mind and convenience. Also, CU might not accept it depending on their policies. Mailing in a check may work, but risk of loss. Many banks and CUs limit mobile deposit to $5K or so per day. after all, how many times a week do you need to move 100K+ between banks with limited options like this? These fees and limits on bank transfers are fairly normal, its just that people dont run into them that often. only down side is there is just about always a fee to send it and often a fee to recieve the wire on the other end as well. No real limits on a wire, typically arrives same day and is pretty safe. ![]() not even 2 months, depending on if the bank goes on calander days or a rolling 30 days, this can be done in just over 2 weeks or done in about 31 days. Wells fargo allows 30K a month it sounds like, online CU likely allows between 25K and 50K a month themselves (rough estimates on lower and upper bounds) so she could transfer about 55K-75K per month and have it done in 2 months without an issue. ![]() however you can typically do the transfer from both ends, meaning she can link wells fargo to the online CU but she can also link the online CU to wells fargo. Bank to bank transfers (ACH transfers) typically take 2-3 days to go through and having limits on them is fairly normal. |
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