Biden wants to follow foolish California and ban freelancing — putting millions out of work

 The Labor Department just imposed 300 pages of new regulations to reclassify many individual contractors as payroll employees.

CNBC claims this could help freelancers “recover lost wages.”

That’s just nonsense.

The new rules will make it harder for some freelancers to support a family.

It will also make it harder for them to do what they want to do.

I know this because I saw what happened in California.

Four years ago, unions got Assemblywoman Lorena Gonzalez to push through a new law that reclassified gig workers.

They were told they’d get higher wages, overtime and other benefits.

Clueless media liked that.

Vox called the law “a big win for workers everywhere.”

Ha! A few months later, Vox Media laid off hundreds of freelancers.

“They expected that all these companies were going to reclassify independent contractors as employees,” freelance musician Ari Herstand told me.

“In reality, they’re just letting them go!”

Herstand was dismayed to learn that when he wants other musicians to join him, he could no longer just write them a check.

“I have to put that drummer on payroll, W-2 him, get workers’ comp insurance, unemployment insurance, payroll taxes!” he complains.

“I have to hire a payroll company.”

California’s anti-freelance law was supposed to protect “abused” Uber and Lyft drivers.

But many like the flexibility of being independent.

“I don’t want a boss to tell me when or where to drive!” one told us.

But union-funded politicians insist they know better.

Gonzalez said, “When you have to take a side job or a third or fourth gig, that’s not flexibility; that’s feudalism!”

What followed was what usually happens when politicians pass bad laws.

Politically connected people pay lawyers and lobbyists to exempt them.

Truck drivers got an exemption from California’s new law.

So did writers, photojournalists, graphic designers, illustrators, musicians (like Herstand) and more than a hundred other professions.

Uber and Lyft got exemptions, too.

“Why is that good law?” I ask.

“Exemption for whoever’s clever enough to get to the politicians.”

“It’s definitely not the solution,” Herstand admits.

“That doesn’t seem like that’s a way to legislate.”

No.

But that’s how it’s done.

When a reporter asked Gonzalez, “What do you have to say to those freelance journalists, those independent contractors, who have now lost their jobs because of your bill?”

The lawmaker sneered, “These aren’t jobs. These are freelance positions that may be three hours a month.”

The arrogance!

People chose these jobs.

Most had other choices.

Unemployment is low.

Freelancers like the flexibility that freelance work provides.

How dare politicians declare, for everyone, that those jobs aren’t good enough?

“They’re embarrassed that they made this huge mistake,” says Herstand.

“They aren’t taking it back,” I point out.

“No politician ever wants to admit that they did something wrong,” he replies.

The results of California’s mistakes are now in.

Even with all the exemptions for the politically connected, freelancers still lost jobs.

A Mercatus Center study found that employment fell by as much as 28% in professions where self-employment was common.

And that’s not because most freelancers got staff jobs with benefits.

Labor-force participation fell, too.

Yet now the US Department of Labor is forcing the rest of America to restrict freelance work, too?

Insane!

It’s a reason we have 50 states.

Not all of us want to be more like California!

Even worse, President Biden wants to go further by getting Congress to pass a union-backed bill called the PRO Act.

It would reclassify workers the same way California did, but without any exemptions!

Don’t politicians ever learn?

No.

Biden says he is eager to be “the most pro-union president in American history.”

John Stossel is the author of “Give Me a Break: How I Exposed Hucksters, Cheats, and Scam Artists and Became the Scourge of the Liberal Media.”

https://nypost.com/2024/04/10/opinion/biden-wants-to-follow-foolish-california-and-ban-freelancing-putting-millions-out-of-work/

Serious flu damage prevented by compound that blocks unnecessary cell death

 As lung cells are killed by the influenza virus, they burst open, releasing molecular signals that trigger the immune cells that can combat the infection. This strategy can be an important red flag that something is wrong; however, if one cell death response, called necroptosis, continues unchecked, it can cause life-threatening injury to lung tissue.

In a study published April 10 in the journal Nature, Tufts University School of Medicine scientists and collaborators present a newly developed compound capable of reversing the course of infection in mice by blocking necroptosis.

There are currently few therapeutic options available to reverse the course of a serious flu infection other than to manage symptoms until the body can combat the virus on its own. With prior evidence showing that lung injury can be caused by influenza-induced necroptosis, the researchers showed that a compound called UH15-38 can safely and efficiently block the key receptor in lung cells undergoing necroptosis without intolerable side effects.

"If you remove necroptosis, you still get restriction of the viral replication without causing the massive damage to the lungs," says Alexei Degterev, an associate professor of developmental, molecular and chemical biology at Tufts University School of Medicine and a co-corresponding author on the study.

"Necroptosis does not appear to be necessary for restricting a viral activity, so if we can block it, we will be able to protect the host by reducing inflammation in the lungs."

Necroptosis is triggered when a cell under duress activates its receptor interacting protein kinase 3 (RIPK3) pathway, thereby attracting immune cells to the area. UH15-38 reduces excessive inflammation by inhibiting the activation of the RIPK3 pathway.

Not only did UH15-38 prove to be well-tolerated in mice, but it successfully prevented any influenza deaths, even when administered up to five days into the course of an infection.

The researchers note that if the results from the mouse studies extend into further preclinical and human trials, compounds like UH15-38 could potentially address the most severe flu infections as well as other viruses that trigger severe respiratory symptoms. The value of the approach is how it addresses the inflammation that is intended to be protective but can do more harm than good.

"While the worst of COVID-19 may be behind us, the credible expectation is that there will be another pandemic that's going to happen and we need something that is going to protect the host independent of how the host is infected," says Degterev. "This work highlights the possibility of achieving such a goal and renews interest in how cell death shapes infections."

Tufts University researchers helped organize the study and provided key insights into the UH15-38 inhibitor, but these results would not have been possible without investigators at multiple institutions—including Fox Chase Cancer Center, the University of Houston, and St. Jude Children's Research Hospital—working closely together.

Degterev and his co-collaborators are now pursuing the second generation of these inhibitors. They are also continuing to test how UH15-38 and related compounds can protect against other respiratory diseases. The commercialization of UH15-38 is being managed by Tufts University's Office for Technology Transfer and Industry Collaboration.

More information: Siddharth Balachandran, Necroptosis blockade prevents lung injury in severe influenza, Nature (2024). DOI: 10.1038/s41586-024-07265-8. www.nature.com/articles/s41586-024-07265-8

https://medicalxpress.com/news/2024-04-flu-compound-blocks-unnecessary-cell.html

Switching out of 'fight' mode: Hormones seen reprogramming metabolism of immune cells

 Cortisone and other related glucocorticoids are extremely effective at curbing excessive immune reactions. But previously, astonishingly little was known about how they exactly do that. A team of researchers from Charité—Universitätsmedizin Berlin, Uniklinikum Erlangen and Ulm University have now explored the molecular mechanism of action in greater detail.

As the researchers report in the journal Nature, glucocorticoids reprogram the metabolism of immune cells, activating the body's natural "brakes" on inflammation. These findings lay the groundwork for development of anti-inflammatory agents with fewer and less severe side effects.

The glucocorticoid cortisone is actually naturally present in the body as cortisol, a stress hormone. The organism releases cortisol to improve the body's responses to stress. Cortisol intervenes in sugar and fat metabolism and affects other parameters, including blood pressure and respiratory and heart rate.

At higher doses, it also inhibits the activity of the immune system, which makes it useful for medical purposes. Due to their excellent efficacy, synthetic glucocorticoid derivates that inhibit inflammation, even more than the natural substance present in the body, are used to treat a wide range of immune-mediated inflammatory diseases. They are among the most widely used medications of all.

Glucocorticoids affect genes, cellular energy sources

However, glucocorticoid-based medications also have side effects, especially at higher doses and when administered for longer periods. These side effects are related to the other effects of the body's own cortisol. They include high blood pressure, osteoporosis, diabetes, and weight gain.

With the aim of developing anti-inflammatory agents with fewer and less severe side effects, a team of researchers led by Prof. Gerhard Krönke, director of the Department of Rheumatology and Clinical Immunology at Charité, has now conducted a closer study of how the immunosuppressive effects of glucocorticoids exactly works.

"It was previously known that glucocorticoids activate a number of genes in different cells of the body," Krönke explains. "But through this mechanism, they mainly activate the resources present in the body. This does not adequately explains its strong immunosuppressive effect.

"In our study, we have now been able to show that glucocorticoids affect more than just the gene expression in immune cells. It also affects the cell´s powerhouses, the mitochondria. And that this effect on cell metabolism is in turn crucial to the anti-inflammatory effects exerted by glucocorticoids."

Swords to plowshares

For the study, the research team focused on macrophages, a type of immune cell responsible for eliminating intruders such as viruses and bacteria. These cells can also play a role in the emergence of immune-mediated inflammatory diseases.

The researchers studied how these immune cells—derived in this case from mice—responded to inflammatory stimuli in a laboratory setting and what effects additional administration of a glucocorticoid had. The researchers observed that in addition to its effect on gene expression, glucocorticoids had a major effect in reversing changes in the cell metabolism that had been initiated by the inflammatory stimuli.

"When macrophages are put into 'fight' mode, they redirect their cellular energy into arming for a fight. Instead of supplying energy, their mitochondria produce the components needed to fight intruders," Krönke says, describing the processes involved.

"Glucocorticoids reverse the process, switching the 'fight' mode back off and turning swords into plowshares, so to speak. A tiny molecule called itaconate plays an especially important role in this."

Itaconate mediates anti-inflammatory effect of glucocorticoids

Itaconate is an anti-inflammatory substance that the body naturally produces inside its mitochondria. Macrophages produce it early on when they are activated so that the inflammatory reaction will subside after a certain period. Generation of this natural immune "brake," however, requires sufficient fuel.

When the cell´s powerhouses are arming up for a fight, that is no longer the case, so itaconate production dwindles to a halt after a while. With normal, short-term inflammation, this timing is effective because the immune response has also subsided in the meantime.

"With a persistent inflammatory stimulus, the drop-off in itaconate production is an issue because there is then no immune 'brake' even though the immune system is still running on all cylinders, eventually contributing to chronic inflammation," explains Dr. Jean-Philippe Auger, a scientist at the Department of Medicine 3—Rheumatology and Immunology at Uniklinikum Erlangen and the first author of the study.

"This is where glucocorticoids intervenes. By reprogramming the mitochondrial function, they ramp up the formation of itaconate in the macrophages, restoring its anti-inflammatory effect."

The search for new active substances

Using animal models for asthma and rheumatoid arthritis, the researchers were able to demonstrate how much the anti-inflammatory effect of glucocorticoids depends on itaconate. Glucocorticoids had no effect in animals that were unable to produce itaconate.

So, if itaconate mediates the immunosuppressant effect of cortisone, wouldn't it be possible to administer itaconate directly, instead of glucocorticoids?

"Unfortunately, itaconate isn't a particularly good candidate as an anti-inflammatory drug, because it's unstable, and due to its high reactivity, it could cause side effects if administered systemically," Krönke explains.

"Aside from that, we assume the processes in humans to be a bit more complex than those in mice. So our plan is to look for new synthetic compounds that are just as effective as glucocorticoids at reprogramming the mitochondrial metabolism inside immune cells, but have fewer and less severe side effects."

More information: Gerhard Krönke, Metabolic rewiring promotes anti-inflammatory effects of glucocorticoids, Nature (2024). DOI: 10.1038/s41586-024-07282-7. www.nature.com/articles/s41586-024-07282-7

https://medicalxpress.com/news/2024-04-body-mode-hormones-reprogram-metabolism.html

New drug prototype regenerates lung tissue

 Pulmonary diseases are a leading cause of morbidity and mortality worldwide. For many progressive lung diseases like idiopathic pulmonary fibrosis (IPF), a key issue is a low supply of new stem cells to repair and reverse damage. These cells are responsible for regenerating and increasing the growth of healthy tissue—without them, lung function decreases and a range of severe illnesses can take hold.

But a team of scientists at Scripps Research and its drug discovery arm, the Calibr-Skaggs Institute for Innovative Medicines, has now developed a lung-targeted, druglike small molecule to stimulate the growth of lung stem cells. These new findings, published in the Proceedings of the National Academy of Sciences, provide a biological proof of concept for activating one of the body's regenerative pathways and restoring damaged lung tissue.

This approach could transform the treatment of severe pulmonary diseases, notably as CMR316—Calibr-Skaggs' similar therapy for treating IPF—is set to enter a phase 1 clinical trial this summer.

"My approach toward regenerative medicine has been figuring out how to promote regenerative, proliferative repair of organs using druglike molecules that act on endogenous stem cell populations," says co-senior author Michael J. Bollong, Ph.D., an associate professor and the Early Career Endowed Roon Chair for Cardiovascular Research in the Department of Chemistry at Scripps Research. "We chose the lung because the stem cell population of the lower airway doesn't regenerate as effectively as one ages."

That means more scar tissue is secreted, which can lead to IPF—a disease that affects up to 20 per 100,000 people worldwide, according to the National Library of Medicine. However, there currently are no available treatment options that regenerate damaged lung tissue.

"Most drugs act by slowing the progression of disease—our approach is to make drugs that control cell fate to stop or reverse the disease process," says Peter G. Schultz, Ph.D., co-senior author and the President and CEO of Scripps Research.

To see whether existing drug mechanisms could increase growth of lung stem cells, the team turned to ReFRAME, a drug repurposing library built by Calibr-Skaggs. ReFRAME permits researchers to rapidly sort through thousands of existing FDA-approved drugs and determine whether they could treat any other major diseases. This approach is particularly useful for cellular systems that aren't easily amenable to large-scale screening campaigns.

"ReFRAME allowed us to understand what the target was immediately, to start understanding how that biology made sense in the context of the lung, and to test the concept directly in vivo," says Bollong.

Using ReFRAME, the team—which also includes Scripps Research and Calibr-Skaggs researchers Sida Shao, Nan Zhang, Sean B. Joseph, Arnab K. Chatterjee and Jeffrey Jian Chen—determined that a drug class known as DPP4 inhibitors could potentially help activate production of lower airway stem cells, called type 2 alveolar epithelial cells (AEC2).

Although DPP4 inhibitors are often used as medications for type 2 diabetes to control blood sugar, the researchers found that the inhibitors promoted production of AEC2 in mice with damaged lungs. However, the dose required when using existing inhibitors for lung repair would be too high and unsafe for humans, meaning it wouldn't be possible to directly repurpose approved inhibitors for clinical use, especially when used in combination with other anti-fibrotic drugs.

"To effectively repair the lungs, the dosing would be roughly 50 to 100 times as much, so we needed to make a drug that inhibited DPP4 in the lung only," explains Bollong. "That's why we went after a lung-targeted and lung-retained approach."

Bollong and his team developed NZ-97, a DPP4 inhibitor that persists in the lungs and promotes AEC2 growth in mice with lung damage. While NZ-97 is a prototype drug, it's chemically similar to CMR316, Calibr-Skagg's drug that will be entering a phase 1 clinical trial in a few months.

Unlike preexisting DPP4 inhibitors, CMR316 will be administered once weekly via a nebulizer—a machine that generates a medicinal mist to inhale—so it's delivered directly to the lungs. The research team also chemically modified these agents to remain in the lungs for long periods, such that the drug selectively inhibits DPP4 only in this organ.

"What that ultimately allowed us to do is have a drug that could be administered at very low doses," Bollong says. In fact, the projected dose for humans is inhaling 1 mg to 2 mg over the span of a couple of minutes once per week. "People have been making DPP4 inhibitors for more than 20 years, so we could leverage that known chemical matter to make a very good version of the drug that's efficacious, lung retained and safe."

Bollong, Schultz, and the rest of the research team are hopeful that CMR316 will also be able to assist with lung damage from a range of other pulmonary illnesses, including influenza, COVID-19 and chronic obstructive pulmonary disease, the third leading cause of death around the globe, according to the World Health Organization.

"IPF makes the most sense as the first disease to investigate because it's driven by a deficiency in this stem cell population," Bollong explains, adding that NZ-97 showed generalizable efficacy across a wide array of lung damage models. "What we also show in this paper is that we've taken stem cells from IPF patient donors and replenish their capacity to grow at an ex vivo format." That's why NZ-97 is a key component in showing how CMR316 works from a pharmacological perspective.

With CMR316 poised to enter the clinic shortly, the research team is also moving forward compounds with novel mechanisms that help heart cells regenerate and repair damage from heart failure, as well as using small molecule drugs to replenish cells in organs ranging from the cornea to the kidney to the colon.

In addition to Bollong and Schultz, authors of the study are Sida Shao, Nan Zhang, Gregory P. Specht, Shaochen You, Lirui Song, Qiangwei Fu, David Huang, Hengyao You, Alain Domissy, Shuangwei Li, Van Nguyen-Tran, Sean B. Joseph, Arnab K. Chatterjee and Jeffrey Jian Chen of Scripps Research; and Jian Shu of Harvard University.

More information: Sida Shao et al, Pharmacological expansion of type 2 alveolar epithelial cells promotes regenerative lower airway repair, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2400077121

https://medicalxpress.com/news/2024-04-drug-prototype-regenerates-lung-tissue.html

'Time For A U.S. STEM Talent Strategy To Compete With China'

 'by Dan Reed & Dario Gil via RealClear Wire,'

U.S. innovation fuels our economic strength and is vital for our national security. Released last earlier this month, the National Science Board’s congressionally mandated State of U.S. Science and Engineering Indicators report shows that an accelerating science, technology, engineering, and math (STEM) talent crisis is imperiling America’s economy and security.

Let’s start with a bit of perspective. The U.S. STEM workforce is now one quarter of the total U.S. workforce – 38 million people at all degree levels who use STEM skills in their jobs, including 19 million skilled technical workers without a bachelor’s degree. That number will only rise as companies expand their STEM workforce and their R&D investments in response to rising global competition. The CHIPS & Science Act is now funding one response to global competition and national security risk -- the reshoring of our semiconductor production.

Meanwhile, key technological sectors, including semiconductors, artificial intelligence, and cybersecurity, face major challenges in filling urgently needed job openings, and making the promise of economic development a reality. Let’s be clear –China is gaining on us, and it has articulated plans to increase its R&D investment even further. Indicators data show that China recently surpassed the United States in research publications and patent applications, and China’s growth in high impact articles is outpacing its overall growth in publications. These overall trends are also true for the specific field of artificial intelligence – a field that is critical to national security. We cannot risk falling behind.

We must address this crisis now. How?

First, we must increase the flow of domestic talent into the STEM workforce. To start, Congress must fully fund the remaining parts of CHIPS & Science Act – investing in developing the STEM workforce, from preK-12 education through skilled technical workers and college STEM graduates to doctoral-level researchers in industry and academia. Sadly, the spending bill that Congress just passed cuts some of our most important science federal agencies, like the National Science Foundation, moving us backwards.

Second, we need new policies that double-down on one of our nation’s greatest strengths: attracting and retaining top STEM talent from around the world, including from countries that are emerging science partners. We must do more to entice and enable science and engineering students to work in the U.S. after they receive their degrees.

Third, we need a modern-day National Defense Education Act (NDEA) to spur private and public collaboration and provide the specific skills and talent needed by American industry.

An NDEA that would: invest in preK-12 STEM education and increase our STEM teacher supply across the country. Build capacity for the gateways into STEM training across the country: community colleges, technical schools, and other geographically and financially accessible institutions. Expand graduate fellowship programs, with a focus on critical and emerging technologies. Create national service programs like the Defense Civilian Training Corps and increase scholarships for low-income individuals. Increase options for foreign-born STEM talent to stay after their education and training and reduce barriers for doing so.

This is a national call-for-action. We need all-hands on deck – no group alone can solve this problem. Business, government, and academia must come together in a collaborative partnership and commitment far beyond the scale in which we are investing now. Otherwise, we risk ceding U.S. science and engineering leadership to China, with deep and lasting negative effects on our national security and our economic competitiveness.

'Dr. Dan Reed is a former Microsoft Executive and currently serves as the chair of the National Science Board (NSB). Reed previously served as Provost at the University of Utah where he now is Presidential Professor of Computational Science and Professor of Computer Science and Electrical & Computer Engineering.

Dr. Darío Gil is the IBM Senior Vice President and Director of Research and a member of the NSB.'

https://www.zerohedge.com/political/its-time-us-stem-talent-strategy-compete-china

Global Bond Selloff Extends in Asia After US CPI: Markets Wrap

 

• Shares in Australia, Japan, and Hong Kong futures all decline
• Treasury 10-year yield tops 4.5% for first time since November

Bonds in Asia fell sharply while Treasuries stabilized after higher-than-expected US inflation data strengthened the case that the Federal Reserve is in no rush to cut interest rates.

Benchmark 10-year yields in Australia and New Zealand climbed by more than 10 basis points. Their Japanese counterpart rose to the highest since November. US government debt steadied in Asia after a selloff on Wednesday lifted the 10-year yield by 18 basis points to above 4.5% for the first time in five months.

https://www.bloomberg.com/news/articles/2024-04-10/stock-market-today-dow-s-p-live-updates

Korean Stocks, Won Fall as Election Results Cloud Reform Outlook

 

• Kospi drops as much as 1.6% as opposition majority gains
• Won weakens vs dollar as hot US inflation stokes risk aversion

South Korean stocks declined after President Yoon Suk Yeol’s party suffered a significant loss in parliamentary elections, likely dealing a blow to his conservative capital market agenda.

The benchmark Kospi fell as much as 1.6% as the market reopened following a holiday for the vote on Wednesday. The won weakened 0.7% to 1,364.85 per dollar, a 17-month low, after stronger-than-expected US inflation data stoked broader risk aversion, strengthening the greenback and overshadowing the impact from the local elections.

https://www.bloomberg.com/news/articles/2024-04-11/korean-stocks-fall-as-ruling-party-suffers-major-election-loss