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Artificial ‘candy canes’ block viruses

Artificial ‘candy canes’ block viruses

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Publication in the Journal of the American Chemical Society

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Credit: L. Hartmann, M. Schelhaas

Viruses are part of the human experience throughout our lives. They cause lots of different illnesses with the current coronavirus pandemic as just one example. While a vaccine does provide effective protection from viral infections, vaccines are only available for a select number of viruses. This is why antiviral drugs need to be found that can prevent or treat a viral infection.

One successful strategy involves special molecules to block viral proteins that would otherwise help the virus to attach to the host cell. Once a virus has attached to the cell surface, it can infect the cell with its genome and reprogram the cell for its own uses. However, many antiviral drugs lose their effect over time, as viruses mutate very quickly and thus often adapt to the medication/antiviral used.

The research team led by HHU Prof. Dr. Laura Hartmann from the Institute of Macromolecular Chemistry and Münster-based Prof. Dr. Mario Schelhaas from the Institute of Cellular Virology working together with Prof. Dr. Nicole Snyder from Davidson College in North Carolina, USA has used the approach of suppressing the initial contact between the virus and the cell in order to stop infection at the onset.

Viruses frequently use special proteins to bind to sugar molecules on the cell surface. Among others, these sugars include long-chain glycosaminoglycans (GAGs), which are strongly negatively charged. One of these GAGs is heparan sulfate. Researchers already knew that GAGs can reduce virus infections if they are added externally. However, natural polysaccharides may have side-effects that are attributed to their own biological function in the organism or to impurities.

The research team is now using the benefits of the GAGs but deactivates their disadvantages. The idea is to use molecules produced artificially and in a controlled fashion, so called ‘glycomimetics’, that are developed at HHU. They comprise a long synthetic scaffold with side chains with small sugar molecules attached. In Düsseldorf, both shorter chains with up to ten lateral sugars (known as ‘oligomers’) and long chains with up to 80 sugars (called ‘glycopolymers’) have been created. In order to simulate the highly charged state of natural GAGs, the chemists coupled sulfate groups to the sugars.

Prof. Schelhaas then used cell cultures to test the antiviral properties of these ‘candy canes’ of varying length at University Hospital Münster. Initially, his team used them against Human Papillomaviruses, which can trigger diseases such as cervical cancer. They discovered that both, the short and long-chain synthetic molecules, have an antiviral effect, but their mode of action is different. As expected, the more effective, long-chain molecules prevented the virus from attaching to cells. In contrast, the short-chain molecules displayed antiviral activity after attachment to the cell, giving rise to the assumption that these molecules are active in the organism for longer.

This is what Prof. Schelhaas has to say: “It is very likely that the long-chain molecules occupy the binding sites of the virus to the cell and thus block those sites. The short-chain molecules apparently do not block these sites. The next step is to test our hypothesis that these molecules prevent the redistribution of proteins in the virus particle so that the viruses cannot infect the cell.”

Effectiveness was also confirmed for the Papillomaviruses in an animal model. The compounds were also active against four other viruses, including Herpes viruses, which can cause cold sores and encephalitis, and Influenza viruses, which cause the flu. Prof. Hartmann explains: “Glycomimetics are thus promising compound molecules that could potentially be used in the fight against a large number of different viruses. The next thing to do is to examine the precise way in which the glycomimetics work and how they can be further optimised.”

Prof. Schelhaas adds: “Further research will focus on how fast viruses may adapt to this new class of compounds. With the short-chain molecules in particular, we are hopeful that viruses will find it harder to launch a counterattack.”

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The project was supported by the German Research Foundation within the framework of funding the Virocarb Research Unit and by the German Federal Ministry of Education and Research as part of funding for the European Infect-ERA consortium HPV-MOTIVA. In addition, the Heine Research Academies (HeRA) at HHU funded the exchange programme with Prof. Snyder’s group.

Original publication

Laura Soria-Martinez, Sebastian Bauer, Markus Giesler, Sonja Schelhaas, Jennifer Materlik, Kevin Janus, Patrick Pierzyna, Miriam Becker, Nicole L. Snyder, Laura Hartmann and Mario Schelhaas, Prophylactic Antiviral Activity of Sulfated Glycomimetic Oligomers and Polymers, J. Am. Chem. Soc. 2020, 142, 11, 5252-5265

DOI: 10.1021/jacs.9b13484

Media Contact
Arne Claussen
arne.claussen@hhu.de

Related Journal Article

http://dx.doi.org/10.1021/jacs.9b13484

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Manufacturing and construction vs. the still-inverted yield curve

  – by New Deal democratProf. Menzie Chinn at Econbrowser makes the point that the yield curve is still inverted, and has not yet eclipsed the longest…

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 - by New Deal democrat


Prof. Menzie Chinn at Econbrowser makes the point that the yield curve is still inverted, and has not yet eclipsed the longest previous time between onset of such an inversion and a recession. So he believes the threat of recession is still on the table.


And he’s correct about the yield curve, although it is getting very long in the tooth. In the past half century, the shortest time between a 10 minus 2 year inversion (blue in the graph below) to recession has been 10 months (1980) and the longest 22 months (2007). For the 10 year minus 3 month inversion (red), the shortest time has been 8 months (1980 and 2001) and the longest has been 17 months (2007):



At present the former yield curve has been inverted for 20.5 months, and the latter for 16.5 months. So if there is no recession by May 1, we’re in uncharted territory as far as the yield curve indicator is concerned.

My view for the past half year or so has been much more cautious. While there has been nearly unprecedented Fed tightening (only the 1980-81 tightening was more severe), on the other hand there was massive pandemic stimulus, and what I described on some occasions as a “hurricane force tailwind” of supply chain unkinking. If the two positive forces have abated, does the negative force of the Fed tightening, which is still in place, now take precedence? Or because interest rates have plateaued in the past year, is it too something of a spent force? Since I confess not to know, because the situation is unprecedented in the modern era for which most data is available, I have highlighted turning to the short leading metrics. Do they remain steady or improve? Or do they deteriorate as they have before prior recessions?

First of all, let me show the NY Fed’s Global Supply Chain Index, which attempts to disaggregate supply sided information from demand side information. A positive value shows relative tightening, a negative loosening:



You can see the huge pandemic tightening in 2020 into 2022, followed by a similarly large loosening through 2023. For the past few months, the Index has been close to neutral, or shown very slight tightness.

Typically in the past Fed tightenings have operated through two main channels: housing and manufacturing, especially durable goods manufacturing.

Let’s take the two in reverse order.

Manufacturing has at very least stalled, and by some measures turned down to recessionary levels.  Last week I discussed industrial production (not shown), which peaked in late 2022 and has continued to trend sideways to slightly negative right through February.

A very good harbinger with a record going back 75 years has been the ISM manufacturing index. Here’s its historical record through about 10 years ago (when FRED discontinued publishing it):



And here is its record for the past several years:



This index was frankly recessionary for almost all of last year. It is still negative, although not so much as before.

Two other metrics with lengthy records are the average hourly workweek in manufacturing (blue, right scale), which is one of the 10 “official” leading indicators, as well as real spending on durable goods (red, measured YoY for ease of comparison, left scale):



As a general rule, if real spending on durable goods turns negative YoY for more than an isolated month, a recession has started (with the peak in absolute terms coming before). Also, since employers generally cut hours before cutting jobs, a decline of about 0.8% of an hour in the average manufacturing workweek has typically preceded a recession - with the caveat in modern times that it must fall to at least roughly 40.5 hours:



The average manufacturing workweek has met the former criteria for the last 9 months, and the latter since November. By contrast, real spending on durable goods was up 0.7% YoY as of the last report for January, and in December had made an all-time record high.

But if some of the manufacturing data has met the historical criteria for a recession warning, it is important to note that manufacturing is less of US GDP than before the year 2000, and had been down more in 2015-16 without a recession occurring.

Further, housing construction has not meaningfully constricted at all. The below graph shows the leading metric of housing permits (another “official” component of the LEI, right scale), together with housing units under construction (gold, *1.2 for scale, right scale), and also real GDP q/q (red, left scale):



Housing permits declined -30% after the Fed began tightening, which has normally been enough to trigger a recession. *BUT* the actual measure of economic activity, housing units under construction, has barely turned down at all. In comparison to past downturns, where typically it had fallen at least 10%, and more often 20%, before a recession had begun, as of last month it was only 2% off peak!

The only other two occasions where housing permits declined comparably with no recession ensuing - 1966 and 1986 - real gross domestic product increased robustly. This was similarly the case in 2023.

An important reason is the other historical reason proppin up expansions: stimulative government spending. Here’s the historical record comparing fiscal surpluses vs. deficits:



Note the abrupt end of stimulative spending in 1937, normally thought to have been the prime driver of the steep 1938 recession. Note also the big “Great Society” stimulative spending in 1966-68, when a downturn was averted (indeed, although not shown in the first graph above, there was an inverted yield curve then as well). Needless to say, there as been a great deal of stimulative fiscal spending since 2020 as well.

Fed tightening typically works by constricting demand. Both government stimulus and the unkinking of supply chains work to stimulate supply. 

All of which leads to the conclusion that, while manufacturing has reacted to the tightening, the *real* measure of construction activity has not, or not sufficiently to be recessionary.

Tomorrow housing permits, starts, and units under construction will all be updated. Unless there is a sharp decline in units under construction, there is no short term recession signal at all.

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Half Of Downtown Pittsburgh Office Space Could Be Empty In 4 Years

Half Of Downtown Pittsburgh Office Space Could Be Empty In 4 Years

Authored by Mike Shedlock via MishTalk.com,

The CRE implosion is picking…

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Half Of Downtown Pittsburgh Office Space Could Be Empty In 4 Years

Authored by Mike Shedlock via MishTalk.com,

The CRE implosion is picking up steam.

Check out the grim stats on Pittsburgh.

Unions are also a problem in Pittsburgh as they are in Illinois and California.

Downtown Pittsburgh Implosion

The Post Gazette reports nearly half of Downtown Pittsburgh office space could be empty in 4 years.

Confidential real estate information obtained by the Pittsburgh Post-Gazette estimates that 17 buildings are in “significant distress” and another nine are in “pending distress,” meaning they are either approaching foreclosure or at risk of foreclosure. Those properties represent 63% of the Downtown office stock and account for $30.5 million in real estate taxes, according to the data.

It also calculates the current office vacancy rate at 27% when subleases are factored in — one of the highest in the country.

And with an additional three million square feet of unoccupied leased space becoming available over the next five years, the vacancy rate could soar to 46% by 2028, based on the data.

Property assessments on 10 buildings, including U.S. Steel Tower, PPG Place, and the Tower at PNC Plaza, have been slashed by $364.4 million for the 2023 tax year, as high vacancies drive down their income.

Another factor has been the steep drop — to 63.5% from 87.5% — in the common level ratio, the number used to compute taxable value in county assessment appeal hearings.

The assessment cuts have the potential to cost the city, the county, and the Pittsburgh schools nearly $8.4 million in tax refunds for that year alone. Downtown represents nearly 25% of the city’s overall tax base.

In response Pittsburgh City Councilman Bobby Wilson wants to remove a $250,000 limit on the amount of tax relief available to a building owner or developer as long as a project creates at least 50 full-time equivalent jobs.

It’s unclear if the proposal will be enough. Annual interest costs to borrow $1 million have soared from $32,500 at the start of the pandemic in 2020 to $85,000 on March 1. Local construction costs have increased by about 30% since 2019.

But the city is doomed if it does nothing. Aaron Stauber, president of Rugby Realty said it will probably empty out Gulf Tower and mothball it once all existing leases expire.

“It’s cheaper to just shut the lights off,” he said. “At some point, we would move on to greener pastures.”

Where’s There’s Smoke There’s Unions

In addition to the commercial real estate woes, the city is also wrestling with union contracts.

Please consider Sounding the alarm: Pittsburgh Controller’s letter should kick off fiscal soul-searching

It’s only March, and Pittsburgh’s 2024 house-of-cards operating budget is already falling down. That’s the clear implication of a letter sent by new City Controller Rachael Heisler to Mayor Ed Gainey and members of City Council on Wednesday afternoon.

The letter is a rare and welcome expression of urgency in a city government that has fallen in complacency — and is close to falling into fiscal disaster.

The approaching crisis was thrown into sharp relief this week, when City Council approved amendments to the operating budget accounting for a pricey new contract with the firefighters union. The Post-Gazette Editorial Board had predicted that this contract — plus two others yet to be announced and approved — would demonstrate the dishonesty of Mayor Ed Gainey’s budget, and that’s exactly what’s happening: The new contract is adding $11 million to the administration’s artificially low 5-year spending projections, bringing expected 2028 reserves to just barely the legal limit.

But there’s still two big contracts to go, with the EMS union and the Pittsburgh Joint Collective Bargaining Committee, which covers Public Works workers. Worse, there are tens — possibly hundreds — of millions in unrealistic revenues still on the books. On this, Ms. Heisler’s letter only scratched the surface.

Similarly, as we have observed, the budget’s real estate tax revenue projections are radically inconsistent with reality. Due to high vacancies and a sharp reduction in the common level ratio, a significant drop in revenues was predictable — but not reflected in the budget. Ms. Heisler’s estimate of a 20% drop in revenues from Downtown property, or $5.3 million a year, may even be optimistic: Other estimates peg the loss at twice that, or more.

Left unmentioned in the letter are massive property tax refunds the city will owe, as well as fanciful projections of interest income that are inconsistent with the dwindling reserves, and drawing-down of federal COVID relief funds, predicted in the budget itself. That’s another unrealistic $80 million over five years.

Pittsburgh exited Act 47 state oversight after nearly 15 years on Feb. 12, 2018, with a clean bill of fiscal health. 

It has already ruined that bill of health.

Act 47 in Pittsburgh

Flashback February 21, 2018Act 47 in Pittsburgh: What Was Accomplished?

Pittsburgh’s tax structure was a much-complained-about topic leading up to the Act 47 declaration. The year following Pittsburgh’s designation as financially distressed under Act 47 it levied taxes on real estate, real estate transfers, parking, earned income, business gross receipts (business privilege and mercantile), occupational privilege and amusements. The General Assembly enacted tax reforms in 2004 giving the city authority to levy a payroll preparation tax in exchange for the immediate elimination of the mercantile tax and the phase out of the business privilege tax. The tax reforms increased the amount of the occupational privilege tax from $10 to $52 (this is today known as the local services tax and all municipalities outside of Philadelphia levy it and could raise it thanks to the change for Pittsburgh).

The coordinators recommended an increase in the deed transfer tax, which occurred in late 2004 (it was just increased again by City Council) and in the real estate tax, which increased in 2015.

Legacy costs, principally debt and underfunded pensions, were the primary focus of the 2009 amended recovery plan. The city’s pension funded ratio has increased significantly from where it stood a decade ago, rising from the mid-30 percent range to over 60 percent at last measurement.

The obvious question? Will the city stick to the steps taken to improve financially and avoid slipping back into distressed status? If Pittsburgh once stood “on the precipice of full-blown crisis,” as described in the first recovery plan, hopefully it won’t return to that position.

The Obvious Question

I could have answered the 2018 obvious question with the obvious answer. Hell no.

No matter how much you raise taxes, it will never be enough because public unions will suck every penny and want more.

On top of union graft, and insanely woke policies in California, we have an additional huge problem.

Hybrid Work Leaves Offices Empty and Building Owners Reeling

Hybrid work has put office building owners in a bind and could pose a risk to banks. Landlords are now confronting the fact that some of their office buildings have become obsolete, if not worthless.

Meanwhile, in Illinois …

Chicago Teachers’ Union Seeks $50 Billion Despite $700 Million City Deficit

Please note the Chicago Teachers’ Union Seeks $50 Billion Despite $700 Million City Deficit

The CTU wants to raise taxes across the board, especially targeting real estate.

My suggestion, get the hell out...

Tyler Durden Mon, 03/18/2024 - 12:10

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Profits over patients: For-profit nursing home chains are draining resources from care while shifting huge sums to owners’ pockets

Owners of midsize nursing home chains harm the elderly and drain huge sums of money from facilities using opaque accounting practices while government…

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The for-profit nursing home sector is growing, and it places a premium on cost cutting and big profits, which has led to low staffing and patient neglect and mistreatment. picture alliance via Getty Images

The care at Landmark of Louisville Rehabilitation and Nursing was abysmal when state inspectors filed their survey report of the Kentucky facility on July 3, 2021.

Residents wandered the halls in a facility that can house up to 250 people, yelling at each other and stealing blankets. One resident beat a roommate with a stick, causing bruising and skin tears. Another was found in bed with a broken finger and a bloody forehead gash. That person was allowed to roam and enter the beds of other residents. In another case, there was sexual touching in the dayroom between residents, according to the report.

Meals were served from filthy meal carts on plastic foam trays, and residents struggled to cut their food with dull plastic cutlery. Broken tiles lined showers, and a mysterious black gunk marred the floors. The director of housekeeping reported that the dining room was unsanitary. Overall, there was a critical lack of training, staff and supervision.

The inspectors tagged Landmark as deficient in 29 areas, including six that put residents in immediate jeopardy of serious harm and three where actual harm was found. The issues were so severe that the government slapped Landmark with a fine of over US$319,000more than 29 times the average for a nursing home in 2021 − and suspended payments to the home from federal Medicaid and Medicare funds.

But problems persisted. Five months later, inspectors levied six additional deficiencies of immediate jeopardy − the highest level.

Landmark is just one of the 58 facilities run by parent company Infinity Healthcare Management across five states. The government issued penalties to the company almost 4½ times the national average, according to bimonthly data that the Centers for Medicare & Medicaid Services first started to make available in late 2022. All told, Infinity paid nearly $10 million in fines since 2021, the highest among nursing home chains with fewer than 100 facilities.

Infinity Healthcare Management and its executives did not respond to multiple requests for comment.

Race to the bottom

Such sanctions are nothing new for Infinity or other for-profit nursing home chains that have dominated an industry long known for cutting corners in pursuit of profits for private owners. But this race to the bottom to extract profits is accelerating, despite demands by government officials, health care experts and advocacy groups to protect the nation’s most vulnerable citizens.

To uncover the reasons why, The Conversation delved into the nursing home industry, where for-profit facilities make up more than 72% of the nation’s nearly 14,900 facilities. The probe, which paired an academic expert with an investigative reporter, used the most recent government data on ownership, facility information and penalties, combined with CMS data on affiliated entities for nursing homes.

The investigation revealed an industry that places a premium on cost cutting and big profits, with low staffing and poor quality, often to the detriment of patient well-being. Operating under weak and poorly enforced regulations with financially insignificant penalties, the for-profit sector fosters an environment where corners are frequently cut, compromising the quality of care and endangering patient health.

Meanwhile, owners make the facilities look less profitable by siphoning money from the homes through byzantine networks of interconnected corporations. Federal regulators have neglected the problem as each year likely billions of dollars are funneled out of nursing homes through related parties and into owners’ pockets.

More trouble at midsize

Analyzing newly released government data, our investigation found that these problems are most pronounced in nursing homes like Infinity − midsize chains that operate between 11 and 100 facilities. This subsection of the industry has higher average fines per home, lower overall quality ratings, and are more likely to be tagged with resident abuse compared with both the larger and smaller networks. Indeed, while such chains account for about 39% of all facilities, they operate 11 of the 15 most-fined facilities.

With few impediments, private investors who own the midsize chains have swooped in to purchase underperforming homes, expanding their holdings even as larger chains divest and close facilities.

“They are really bad, but the names − we don’t know these names,” said Toby Edelman, senior policy attorney with the Center for Medicare Advocacy, a nonprofit law organization.

In response to The Conversation’s findings on nursing homes and request for an interview, a CMS spokesperson emailed a statement that said the CMS is “unwavering in its commitment to improve safety and quality of care for the more than 1.2 million residents receiving care in Medicare- and Medicaid-certified nursing homes.”

“We support transparency and accountability,” the American Health Care Association/National Center for Assisted Living, a trade organization representing the nursing home industry, wrote in response to The Conversation‘s request for comment. “But neither ownership nor line items on a budget sheet prove whether a nursing home is committed to its residents.”

Ripe for abuse

It often takes years to improve a poor nursing home − or run one into the ground. The analysis of midsize chains shows that most owners have been associated with their current facilities for less than eight years, making it difficult to separate operators who have taken long-term investments in resident care from those who are looking to quickly extract money and resources before closing them down or moving on. These chains control roughly 41% of nursing home beds in the U.S., according to CMS’s provider data, making the lack of transparency especially ripe for abuse.

A churn of nursing home purchases even during the pandemic shows that investors view the sector as highly profitable, especially when staffing costs are kept low and fines for poor care can easily be covered by the money extracted from residents, their families and taxpayers.

A March 2024 study from Lehigh University and the University of California, Los Angeles also shows that costs were inflated when nursing home owners switched to contractors they controlled directly or indirectly. Overall, spending on real estate increased 20.4% and spending on management increased 24.6% when the businesses were affiliated, the research showed.

“This is the model of their care: They come in, they understaff and they make their money,” said Sam Brooks, director of public policy at the Consumer Voice, a national resident advocacy organization. “Then they multiply it over a series of different facilities.”

This is a condensed version of an article from The Conversation’s investigative unit. To find out more about the rise of for-profit nursing homes, financial trickery and what could make the nation’s most vulnerable citizens safer, read the complete version.

Campbell is an adjunct assistant professor at Columbia University and a contributing writer at the Garrison Project, an independent news organization that focuses on mass incarceration and criminal justice.

Harrington is an advisory board member of the nonprofit Veteran's Health Policy Institute and a board member of the nonprofit Center for Health Information and Policy. Harrington served as an expert witness on nursing home litigation cases by residents against facilities owned or operated by Brius and Shlomo Rechnitz in the past and in 2022. She also served as an expert witness in a case against The Citadel Salisbury in North Carolina in 2021.

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