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May 30 2024 Massachusetts General Hospital

A new study led by investigators from Mass General Cancer Center, a founding member of the Mass General Brigham healthcare system, reveals that statins-;commonly used cholesterol-lowering drugs-;may block a particular pathway involved in the development of cancer that results from chronic inflammation. The findings are published in Nature Communications.

"Chronic inflammation is a major cause of cancer worldwide," said senior author Shawn Demehri, MD, PhD, a principal investigator at the Center for Cancer Immunology and Cutaneous Biology Research Center of Massachusetts General Hospital and an associate professor of Dermatology at Harvard Medical School. "We investigated the mechanism by which environmental toxins drive the initiation of cancer-prone chronic inflammation in the skin and pancreas," says Demehri, who is also the Bob and Rita Davis Family MGH Research Scholar 2023-2028. "Furthermore, we examined safe and effective therapies to block this pathway in order to suppress chronic inflammation and its cancer aftermath."

Demehri and his colleagues' study relied on cell lines, animal models, human tissue samples and epidemiological data. The group's cell-based experiments demonstrated that environmental toxins (such as exposure to allergens and chemical irritants) activate two connected signaling pathways called the TLR3/4 and TBK1-IRF3 pathways. This activation leads to the production of the interleukin-33 (IL-33) protein, which stimulates inflammation in the skin and pancreas that can contribute to the development of cancer.

When they screened a library of U.S. Food and Drug Administration–approved drugs, the researchers found that a statin, pitavastatin, effectively suppresses IL-33 expression by blocking the activation of the TBK1-IRF3 signaling pathway. In mice, pitavastatin suppressed environmentally-induced inflammation in the skin and the pancreas and prevented the development of inflammation-related pancreatic cancers.

In human pancreas tissue samples, IL-33 was over-expressed in samples from patients with chronic pancreatitis (inflammation) and pancreatic cancer compared with normal pancreatic tissue. Also, in analyses of electronic health records data on more than 200 million people across North America and Europe, use of pitavastatin was linked to a significantly reduced risk of chronic pancreatitis and pancreatic cancer.

The findings demonstrate that blocking IL-33 production with pitavastatin may be a safe and effective preventive strategy to suppress chronic inflammation and the subsequent development of certain cancers. Next, we aim to further examine the impact of statins in preventing cancer development in chronic inflammation in liver and gastrointestinal tract and to identify other novel, therapeutic approaches to suppress cancer-prone chronic inflammation"

Shawn Demehri, MD, PhD, senior author Source:

Massachusetts General HospitalJournal reference:

Park, J. H., et al. (2024). Statin prevents cancer development in chronic inflammation by blocking interleukin 33 expression. Nature Communications. doi.org/10.1038/s41467-024-48441-8.

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Entertainment

Lily Allen says she had her children for ‘all the wrong reasons’

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Lily Allen says she had her children for 'all the wrong reasons'

Lily Allen says she had her children “for all the wrong reasons,” at a “high pressure” point in her career when she felt “overwhelmed”.

The singer and actress had her two daughters, Marnie, 12 and Ethel, 11, with her ex-husband Sam Cooper when she was in her mid-20s.

By the time she became a mum, she’d already had hit singles including Smile and The Fear, released two studio albums and received a Brit Award for best British female solo artist.

Speaking about motherhood on the BBC podcast Miss Me?, which Allen hosts with her long-time friend Miquita Oliver, she said: “I think I had children for all the wrong reasons, really.

“Because I was yearning for unconditional love, which I haven’t felt in my life since I was a child.”

The now 39-year-old star added: “And also, my career was at such high speed, high pressure, and I felt like very overwhelmed by what was happening. I just didn’t get much respite you know?

“And I felt like the only way to stop people hassling me was to say, ‘It’s not about me, actually this is about this other person that’s inside me’.

When asked by Oliver if it worked, Allen says: “Yeah, they did leave me alone. I don’t think I really understood what was happening, what I got myself into.”

The daughter of actor Keith Allen and film producer Alison Owen, she went on to discuss her own childhood.

“My mum, bless her, had children really early as well, and she really struggled. But she doesn’t really talk about the struggle. And so… She inadvertently gaslit me into thinking it was, you know, easy.

“You just sort of throw the kid over your shoulder and you get on with it.

“Her job was very static, and in one place and went to an office and mine wasn’t like that at all. It wasn’t easy. It just wasn’t easy.”

Lily Allen is married to Stranger Things star David Harbour
Image:
Allen is married to Stranger Things star David Harbour

The ‘nasty scars’ caused by absent parents

Allen previously told the Radio Times podcast that while she loves her children, having them “ruined her career”.

She said her decision to prioritise them over her pop career was a decision she made so as not to inflict the “nasty scars” of being an “absent” parent onto them.

She also said the myth of having it all “really annoyed” as it simply was not true.

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Allen, whose younger brother is Game Of Thrones actor Alfie Allen, married Stranger Things star David Harbour in 2020.

Away from her music career, Allen has branched out into acting over the last few years, starring in two plays in London’s West End, and winning a role in Sky drama Dreamland last year.

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Environment

JB Hunt launches first electric aftermarket semi truck route in Arizona

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JB Hunt launches first electric aftermarket semi truck route in Arizona

Following successful inbound implementations in the Pacific Northwest, North Carolina, and Mexico, Daimler Trucks North America (DTNA) is expanding the reach of its electric semi fleet into Arizona with long-time associate JB Hunt.

JB Hunt will add the new Freightliner eCascadia electric semi to its Arizona fleet immediately, and put it to work delivering aftermarket truck parts from DTNA’s parts distribution center (PDC) in Phoenix to multiple DTNA dealers along a dedicated route.

The electric Freightliner truck is expected to cover approximately 100 miles in a given day before heading “home” to a Detroit eFill charger installed at Daimler’s Phoenix facility.

This milestone marks the first all-electric route in the DTNA aftermarket parts distribution network, significantly reducing carbon emissions and setting a precedent for future sustainable outbound logistics operations.

“This solution with DTNA is a great example of our commitment to supporting customers’ efforts to reduce their carbon footprint and work towards energy transition,” explains Greer Woodruff, executive vice president of safety, sustainability and maintenance at JB Hunt. “JB Hunt owns and operates several eCascadias on behalf of customers, and our drivers have really enjoyed their in-cab experience. As customer interest continues to grow, we are here to enable their pursuit for a more sustainable supply chain in the most economic means possible.”

Daimler is analyzing future expansion opportunities throughout its internal parts distribution and logistics with an eye on electrifing additional routes and further reducing the carbon footprint of its logistics operations.

JB Hunt will evaluate its utilization of the charging station for other customers in the area, eventually enabling fully integrated zero-emission vehicle solutions into its 3PL fleets.

SOURCE | IMAGES: Daimler Trucks North America.

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Technology

Intel’s wild week leaves Wall Street more uncertain than ever about chipmaker’s future

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Intel's wild week leaves Wall Street more uncertain than ever about chipmaker's future

Intel CEO Patrick Gelsinger speaks at the Intel Ocotillo Campus in Chandler, Arizona, on March 20, 2024. 

Brendan Smialowski | AFP | Getty Images

It was quite a week for Intel.

The chipmaker, which has lost over half its value this year and last month had its worst day on the market in 50 years after a disappointing earnings report, started the week on Monday by announcing that it’s separating its manufacturing division from the core business of designing and selling computer processors.

And late Friday, CNBC confirmed that Qualcomm has recently approached Intel about a takeover in what would be one of the biggest tech deals ever. It’s not clear if Intel has engaged in conversations with Qualcomm, and representatives from both companies declined to comment. The Wall Street Journal was first to report on the matter.

The stock rose 11% for the week, its best performance since November.

The rally provides little relief to CEO Pat Gelsinger, who has had a tough run since taking the helm in 2021. The 56-year-old company lost its long-held title of world’s biggest chipmaker and has gotten trounced in artificial intelligence chips by Nvidia, which is now valued at almost $3 trillion, or more than 30 times Intel’s market cap of just over $90 billion. Intel said in August that it’s cutting 15,000 jobs, or more than 15% of its workforce.

But Gelsinger is still calling the shots and, for now, he says Intel is pushing forward as an independent company with no plans to spin off the foundry. In a memo to employees on Monday, he said the two halves are “better together,” though the company is setting up a separate internal unit for the foundry, with its own board of directors and governance structure and the potential to raise outside capital.

Intel CEO Pat Gelsinger speaks while showing silicon wafers during an event called AI Everywhere in New York, Thursday, Dec. 14, 2023.

Seth Wenig | AP

For the company that put the silicon in Silicon Valley, the road to revival isn’t getting any smoother. By forging ahead as one company, Intel has to two clear two gigantic hurdles at once: Spend more than $100 billion through 2029 to build chip factories in four different states, while simultaneously gaining a foothold in the AI boom that’s defining the future of technology.

Intel expects to spend roughly $25 billion this year and $21.5 billion next year on its foundries in hopes that becoming a domestic manufacturer will convince U.S. chipmakers to onshore their production rather than relying on Taiwan Semiconductor Manufacturing Company (TSMC) and Samsung.

That prospect would be more palatable to Wall Street if Intel’s core business was at the top of its game. But while Intel still makes the majority of processors at the heart of PCs, laptops, and servers, it’s losing market share to Advanced Micro Devices and reporting revenue declines that threaten its cash flow.

‘Next phase of this foundry journey’

With challenges mounting, the board met last weekend to discuss the company’s strategy.

Monday’s announcement on the new governance structure for the foundry business served as an opening salvo meant to convince investor that serious changes are underway as the company prepares to launch its manufacturing process, called 18A, next year. Intel said it has seven products in development and that it landed a giant customer, announcing that Amazon would use its foundry to produce a networking chip.

“It was very important to say we’re moving to the next phase of this foundry journey,” Gelsinger told CNBC’s Jon Fortt in an interview. “As we move to this next phase, it’s much more about building efficiency into that and making sure that we have good shareholder return for those significant investments.”

Still, Gelsinger’s foundry bet will take years to pay off. Intel said in the memo that it didn’t expect meaningful sales from external customers until 2027. And the company will also pause its fabrication efforts in Poland and Germany “by approximately two years based on anticipated market demand,” while pulling back on its plans for its Malaysian factory. 

TSMC is the giant in the chip fab world, manufacturing for companies including Nvidia, Apple and Qualcomm. Its technology allows fabless companies — those that outsource manufacturing — to make more powerful and efficient chips than what’s currently possible at volume inside Intel’s factories. Even Intel uses TSMC for some of its high-end PC processors.

Intel hasn’t announced a significant traditional American semiconductor customer for its foundry, but Gelsinger said to stay tuned.

“Some customers are reluctant to give their names because of the competitive dynamics,” Gelsinger told Fortt. “But we’ve seen a large uptick in the amount of customer pipeline activity we have underway.”

Prior to the Amazon announcement, Microsoft said earlier this year it would use Intel Foundry to produce custom chips for its cloud services, an agreement that could be worth $15 billion to Intel. Microsoft CEO Satya Nadella said in February that it would use Intel to produce a chip, but didn’t provide details. Intel has also signed up MediaTek, which primarily makes lower-end chips for mobile phones.

U.S. President Joe Biden listens to Intel CEO Pat Gelsinger as he attends the groundbreaking of the new Intel semiconductor manufacturing facility in New Albany, Ohio, U.S., September 9, 2022.

Joshua Roberts | Reuters

Backed by the government

Intel’s biggest champion at the moment is the U.S. government, whish is pushing hard to secure U.S.-based chip supply and limit the country’s reliance on Taiwan.

Intel said this week that it received $3 billion to build chips for the military and intelligence agencies in a specialized facility called a “secure enclave.” The program is classified, so Intel didn’t share specifics. Gelsinger also recently met with Commerce Secretary Gina Raimondo, who is loudly promoting Intel’s future role in chip production.

Earlier this year, Intel was awarded up to $8.5 billion in CHIPS Act funding from the Biden administration and could receive an additional $11 billion in loans from the legislation, which was passed in 2022. None of the funds have been distributed yet. 

“At the end of the day, I think what policymakers want is for there to be a thriving American semiconductor industry in America,” said Anthony Rapa, a partner at law firm Blank Rome who focuses on international trade.

For now, Intel’s biggest foundry customer is itself. The company started reporting the division’s finances this year. For the latest quarter, which ended in June, it had an operating loss of $2.8 billion on revenue of $4.3 billion. Only $77 million in revenue came from external customers.

Intel has a goal of $15 billion in external foundry revenue by 2030.

While this week’s announcement was viewed by some analysts as the first step to a sale or spinoff, Gelsinger said that it was partially intended to help win new customers that may be concerned about their intellectual property leaking out of the foundry and into Intel’s other business.

“Intel believes that this will provide external foundry customers/suppliers with clearer separation,” JPMorgan Chase analysts, who have the equivalent of a sell rating on the stock, wrote in a report. “We believe this could ultimately lead to a spin out of the business over the next few years.”

No matter what happens on that side of the house, Intel has to find a fix for its main business of Core PC chips and Xeon server chips.

Intel’s client computing group — the PC chip division — reported about a 25% drop in revenue from its peak in 2020 to last year. The data center division is down 40% over that stretch. Server chip volume decreased 37% in 2023, while the cost to produce a server product rose.

Intel has added AI bits to its processors as part of a push for new PC sales. But it still lacks a strong AI chip competitor to Nvidia’s GPUs, which are dominating the data center market. The Futurum Group’s Daniel Newman estimates that Intel’s Gaudi 3 AI accelerator only contributed about $500 million to the company’s sales over the last year, compared with Nvidia’s $47.5 billion in data center sales in its latest fiscal year.

Newman is asking the same question as many Intel investors about where the company goes from here.

“If you pull these two things apart, you go, ‘Well, what are they best at anymore? Do they have the best process? Do they have the best design?'” he said. “I think part of what made them strong was that they did it all.”

— CNBC’s Rohan Goswami contributed to this report

WATCH: CNBC’s full interview with Intel CEO Pat Gelsinger

Watch CNBC's full interview with Intel CEO Pat Gelsinger

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