Insights from a rare genetic disease may help treat multiple myeloma

A new class of drugs for blood cancers such as leukemia and multiple myeloma is showing promise. But it is hobbled by a problem that also plagues other cancer drugs: targeted cells can develop resistance. Now scientists have found that insights into a rare genetic disease known as NGLY1 deficiency could help scientists understand how that resistance works — and potentially how drugs can outsmart it.

A protein called Nrf1 (shown in white in these mouse cells) can hamper promising drugs for blood cancers, but now researchers have found a possible workaround to shut Nrf1 down.
Credit: The American Chemical Society

A new class of drugs for blood cancers such as leukemia and multiple myeloma is showing promise. But it is hobbled by a problem that also plagues other cancer drugs: targeted cells can develop resistance. Now scientists, reporting in ACS Central Science, have found that insights into a rare genetic disease known as NGLY1 deficiency could help scientists understand how that resistance works — and potentially how drugs can outsmart it.

A class of compounds called proteasome inhibitors that include bortezomib and carfilzomib — both approved by the U.S. Food and Drug Administration — have been effective at treating certain types of blood cancers. The drugs work by jamming some of cancer cells’ machinery to induce cell death. But the drugs have been limited by cancer cells ability to development resistance, as well as the inhibitors inability to fight solid tumors effectively. Studies have suggested that resistance could be linked to a protein called Nrf1. When proteasome inhibitors go into action, Nrf1 is spurred into overdrive to restore the cells’ normal activities and keep them alive. If researchers could figure out how to block Nrf1, they might be able to address the resistance problem. Carolyn Bertozzi and colleagues, through studying NGLY1 deficiency, a seemingly unrelated condition, may have hit upon an approach to do this.

The researchers were investigating how lacking the enzyme NGLY1 causes a host of debilitating symptoms. They found that NGLY1 is responsible for activating Nrf1, the protein that is suspected of weakening proteasome inhibitors’ effectiveness against cancer. Further testing showed that dampening NGLY1 allowed a proteasome inhibitor to continue doing its work killing cancer cells without interference from Nrf1. This finding, the authors note, holds great promise for the development of combination therapeutics for blood cancers in the future.

[“Source-sciencedaily”]

10 Winning Entrepreneur Insights That May Surprise You

Every aspiring entrepreneur would love to be the next Mark Zuckerberg or Jeff Bezos, but most have no idea what really sets these guys apart from all the rest. Conventional wisdom has them looking for a painful problem, a very large opportunity, and minimal competitive barriers to entry. In reality, most great entrepreneurs find these necessary, but not sufficient for the big win.

They think outside the box, with a sometimes surprising set of strategies, as outlined in a new book, “Think Bigger,” by Michael Sonnenfeldt. He has collected in-the-trenches intelligence and lessons from his TIGER 21 group of over 500 entrepreneurs and executives around the world. Each has amassed $10 million or more in personal assets, and is willing to share their insights with others.

Sonnenfeldt presents a rich array of strategies in his forty lessons from the trenches, including the following paraphrased insights that I find often overlooked or even rejected, based on my years of experience mentoring entrepreneurs:

  1. Experience at a first-rate company is really valuable. Good big companies provide the training, mentoring, and experience managing teams that entrepreneurs need, but can’t afford. In addition, you can learn much about business principles, and your own capabilities, from being surrounded by many intense, ambitious, and super-smart peers.
  2. Entrepreneurship is rarely about just making money. The best entrepreneurs are committed to fixing a problem, or advancing a purpose, and making money is only used as a validation of their insight. Any money made is typically poured back into the cause, rather than relished for a high-class lifestyle or extravagances by the entrepreneur.
  3. Self-control beats passion for long term satisfaction. Passion often leads to a need for instant gratification. Most successful entrepreneurs either learn or are born with the capacity to delay gratification for critical periods in their lives. Even after success, they use self-control to continue to live modestly, and plow their profits back into business.
  4. Think twice before investing with friends and family. Some are so self-centered that they see family and friends as an easy source of capital. Smarter entrepreneurs know that nothing can bring more embarrassment, resentment, and peril to relationships with people you love and respect than losing their money. Don’t jeopardize key relationships.
  5. You are never to smart or too old for a mentor. In case you think mentors are only for “wimps,” you should know that Bill Gates always revered the guidance he received from Warren Buffet on many corporate matters. Most successful business people, whether retired or still active, love to share the wisdom they gained from their own experience.
  6. Entrepreneurial skills can limit investing success. Entrepreneurs and investors are different kinds of people, inside and out. Smart investors diversify their exposure across multiple assets; if any one of these fails, they are still in the game. A true entrepreneur makes one big bet on a new and untested asset, normally against conventional wisdom.
  7. Apply business skills to solve social problems. Social entrepreneurship is on the rise, with the advent of Millennials and a total world view. Companies that pursue socially relevant goals as part of their mission have the potential to generate double-bottom-line results – a financial return as well as a social benefit. One plus one can now equal three.
  8. Skip conservative – be optimistic, even delusional.  The best entrepreneurs just believe they can make it happen – even though conventional logic would peg the risk as being off the charts. Professional investors dismiss founders who give “conservative” financial projections, and usually make less. Shoot for the moon – you may hit it.
  9. Surround yourself with people who are smarter than you. Too many entrepreneurs have a tendency to overrate their personal skills and wisdom, and seek out people who won’t challenge them. The smartest ones acknowledge their weaknesses, and find people who complement their skills, from whom they can learn and delegate authority.
  10. Resilience and determination generally beat IQ. We all know of successful businesses started by entrepreneurs who dropped out of school, while MBAs get no premium with investors. According to most experts, “street smarts” (experience) trump “book smarts” (intelligence) every time, especially if accompanied with a large dose of grit.

Whether you are already a seasoned entrepreneur, or just starting out, I recommend that you regularly strive to think bigger and outside the box, starting with the lessons from others who have been there and done that, and emerged successfully. We need you then to contribute to the next set of winning strategies for the next generation of entrepreneurs.

[“Source-alleywatch”]

Coolpad may launch Cool Play 6 with 6GB of RAM in India on August 20

Coolpad may launch Cool Play 6 with 6GB of RAM in India on August 20

Coolpad is all set to unveil the Cool Play 6 in India on August 20. The smartphone was launched in China back in May for a price of 1,499 Yuan which roughly translates to around Rs 15,000. The smartphone was heavily marketed as a gaming smartphone in China and was launched in two color options – namely Soft Gold and Black.

Coolpad has been teasing the launch of the Play 6 on its Facebook page with the tagline “Livetoplay” and posts such as “6 is not just a number anymore! It is a new era and new benchmark. Monster is all set for 20th Aug. The thrilling power, the invincible. Stay tuned to know more. #LiveToPlay”.

The Play 6 is set to compete with the likes of the Moto G5 Plus and Xiaomi Redmi Note 4. It comes with a metal unibody design, a dual camera setup at the rear, the latest version of Android and fairly high end hardware for the price.

The Play 6 is powered by the Qualcomm Snapdragon 653 processor paired with 6GB of RAM and a 4,060mAh battery that the company claims can deliver 252 hours of standby time, 9 hours of internet browsing, 8 hours of video watching and 6 hours of gaming.

Additionally, the Play 6 comes with a 5.5-inch Full HD display with a resolution of 1080 x1920, 64GB of internal storage expandable via a miscroSD card, a rear mounted fingerprint scanner and a USB Type C port for charging and data transfer. It supports 4G LTE, dualSIMs, Wi-Fi, Bluetooth, and GPS.

On the imaging front, the Cool Play 6 comes with a dual camera setup at the rear – a primary 13MP RGB (color) sensor paired with a secondary 13MP monochrome (black and white) sensor with a dual-LED flash. Both sensors have an aperture of f/2.0. The secondary sensor allows for the capture of images with depth of field information. On the front, there is an 8MP sensor with an aperture of f/2.2 for selfies.

[“Source-indiatoday”]

Xiaomi 5X could be the first smartphone to launch under the Lanmi brand, may launch on July 26

Image result for Xiaomi 5X could be the first smartphone to launch under the Lanmi brand, may launch on July 26Picture Courtesy: Mydrivers.com

Xiaomi is working to bring its third sub-brand after Redmi and Mi, which will reportedly be called – Lanmi, confirmed a Chinese micro blogging site – Weibo. As reported earlier, Xiaomi is said to be have already started working on a smartphone which the company is expected to launch under the Lanmi brand. The smartphone could most probably be the – Xiaomi X1. But, a new report making rounds on the web hints that the first smartphone under the Lanmi brand could be – Xiaomi 5X.

Reports suggest that Xiaomi could launch the smartphone on July 26. But there’s no official confirmation by the company as of now. Xiaomi 5X aka Xiaomi X1 has been subjected to several leaks and rumours already and hints that the device may come with dual-camera setup, antenna lines, and LED flash, which will be placed right next to the dual cameras at the back.

The new leak comes in the form of a poster, which shows the device itself. The poster also reveals a lot about the device, starting from its complete specs, and even the price. It is said that the upcoming Xiaomi 5X could be a mid-ranged smartphone. On the pricing front, the upcoming Xiaomi Mi 5X is likely to be priced at CNY 1,999, which is approximately Rs 19,000. This is a tentative pricing detail, and may be revised at the time of launch.

Also Read: Xiaomi’s new sub-brand could be called Lanmi

As per the specifications, the leak hints that the Xiaomi 5X may come with a 5.5-inch display and may run on the latest Android Nougat operating system. However, the new leak reveals no details about the resolution of the display, but a previous leak claimed that it will most likely end up being 1080p, much like many other mid-range phones from Xiaomi.

The smartphone is further expected to be powered by Qulacomm’s Snapdragon 625 processor and may be coupled with 4GB of RAM and 64GB of internal storage. However, a previous leak suggested that the smartphone – Xiaomi 5X may come with Snapdragon 660. So, we aren’t sure about the authencity of the newly leaked poster, and chances are that the specs might change in the final product.

Furthermore, Xiaomi 5X is expected to come with dual cameras (as tipped by another rumour earlier) at the back and include a 5-megapixel sensor on the front. On the design front, the upcoming Xiaomi phone is expected to feature an all-metal body that looks fairly premium, despite being a mid-ranged smartphone.

Meanwhile, the Chinese smartphone maker is also planning to launch the successors of Redmi 4, Redmi Note 4 and Redmi 4A. In the last couple of days, there have been several rumours about the Redmi 5, Redmi 5A and Xiaomi Redmi Note 5 and all of them suggest that all the three handsets will although boast a full-metal body design much like its successors, but, the camera and hardware may see a major refresh.

A report by a Chinese news website – MyDrivers leaked two weeks ago reveals that the new brand as highlighted earlier is supposed to focus on offline sale strategy mainly, unlike Redmi and Mi that aims at online sales. The company is further said to compete with companies like Oppo and Vivo, which are majorly dependent of offline sale.

[“Source-indiatoday.”]