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Prepare for the next supply chain disruption

[Vienna, May 12, 2022] Researchers at the Complexity Science Hub Vienna (CSH) created a complete representation of Hungary’s economy. They mapped the…

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[Vienna, May 12, 2022] Researchers at the Complexity Science Hub Vienna (CSH) created a complete representation of Hungary’s economy. They mapped the entire country’s production network, including literally all of the relevant firms and all of the supply relationships with their clients and customers. With such detailed knowledge of the economy, they can compute its systemic risks.

Credit: CSHVienna

[Vienna, May 12, 2022] Researchers at the Complexity Science Hub Vienna (CSH) created a complete representation of Hungary’s economy. They mapped the entire country’s production network, including literally all of the relevant firms and all of the supply relationships with their clients and customers. With such detailed knowledge of the economy, they can compute its systemic risks.

“By viewing the economy as a network of all companies and their mutual relationships, we can now rethink economics. In particular, one can compute the risks associated with supply chain disruptions, which can be significant,” says Stefan Thurner, CSH president and co-author of the study that just appeared in Scientific Reports. “This allows us to quantify the economic systemic risk of each company within a country.”

Using a unique dataset of value-added tax (VAT) information – a general tax that, in principle, is applied to all goods and services –, the team was able to reconstruct the production processes and the supply relationships between companies to an unprecedented extent and determine how each enterprise was affected by supply chain disruptions.

“This is the first time the supply chain vulnerability of a country has been calculated at such a detailed, granular level,” states the first author of the paper, Christian Diem.

“Our approach demonstrates that the real economy cannot be seen as a collection of separate supply chains. It’s a tightly connected network that has a strongly connected component, forming the center of the network, and that contains 26 percent of all companies,” adds Diem. “Our findings indicate that only a few firms pose a substantial risk to the overall economy.”

 

Novel approach

The researchers propose a new methodology for calculating the economic systemic risk of companies. The method not only considers all buyer-supplier relationships between businesses, but also other factors, such as the production process of each enterprise, the supply transaction’s importance, and the firm’s value in the overall production of the economy.

The scientists reconstructed the intricate production network of Hungary based on VAT data from more than 91.000 companies provided by the Hungarian Central Bank. Their most surprising finding was the vulnerability of the Magyar economy. It could be shaken by just a handful of enterprises connected by a network of highly critical supply chain relations.

According to the study, the 32 top high-risk companies, which represent 0.035 percent of the analyzed Hungarian enterprises, display an extremely high systemic risk of about 23 percent. “This means that, in the short term, about 23 percent of the national production could be adversely affected if firms cannot adjust their supply relations by finding new suppliers and customers fast enough,” Diem explains.

In addition, almost 75 percent of the national systemic risk is concentrated on only 100 high-risk companies. “Large scale snowball or domino effects are likely caused by one of these 100 firms, while the other 99% enterprises are of marginal systemic relevance.”

 

Policy Implications

The researchers point out that the results have a number of policy implications.

“Using our model, government institutions could identify and monitor the weak spots of the economy – those critical companies that, in case of default, could cause system-wide damage. Once those weaknesses are known, one can consider what can and should be done to fix them and make the system more resilient. We cannot see the dangers of systemic risk without knowing the weaknesses,” explains Thurner.

“Historically, economists argued in favor of regulating the financial system more strongly than the real economy because the systemic risk in the financial system was deemed to be much higher than in the rest of the economy. However, the recent supply chain crises and our results show that systemic risk is substantial in the real economy,” adds Diem.

In addition, the paper suggests introducing larger inventory buffers for risky companies and making firms aware of their economic systemic risk in the system. “Companies might become more sustainable if they know which supply lines are reliable,” Thurner argues. With the new methodology, government institutions could take a more proactive and transparent approach to ensure that supply chains are resilient.

 

The pandemic effect

Business operations in countries around the world have been fundamentally altered by the Covid-19 pandemic. The pandemic has negatively impacted supply chains in the past two years, resulting in shortages in a variety of sectors, including food production, vaccine supply, computer chip manufacturing, and automobile production, according to the paper.

As countries try to move back towards some level of normalization, governments may use VAT data to identify the most vulnerable – and resilient – companies when it comes to supply chains. “It’s impossible for decision-makers to manage economic systemic risks proactively without understanding which companies pose an exceptionally high risk to the entire economy in case of their temporary failure,” the scientists point out.

In the context of current discussions about gas rationing in some EU countries as a consequence of the war in Ukraine, Diem notes that some of the 32 top high-risk companies in the study are in the chemical sector. “These firms, which rely heavily on natural gas for their production, should be – at any cost – protected from gas supply shortages since they will have potentially huge snowball effect on the entire economy.”

 

About the CSH

The mission of Complexity Science Hub Vienna is to host, educate, and inspire complex systems scientists dedicated to making sense of Big Data to boost science and society. Scientists at the Hub develop methods for the scientific, quantitative, and predictive understanding of complex systems.

The CSH is a joint initiative of AIT Austrian Institute of Technology, Central European University CEU, Danube University Krems, Graz University of Technology, Medical University of Vienna, TU Wien, VetMedUni Vienna, Vienna University of Economics and Business, and Austrian Economic Chambers (WKO).

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The Battle For Control Of Your Mind

The Battle For Control Of Your Mind

Authored by Aaron Kheriaty via The Brownstone Institute

In his classic dystopian novel 1984, George…

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The Battle For Control Of Your Mind

Authored by Aaron Kheriaty via The Brownstone Institute

In his classic dystopian novel 1984, George Orwell famously wrote, “If you want a picture of the future, imagine a boot stamping on a human face—for ever.” This striking image served as a potent symbol for totalitarianism in the 20th Century. But as Caylan Ford recently observed, with the advent of digital health passports in the emerging biomedical security state, the new symbol of totalitarian repression is “not a boot, but an algorithm in the cloud: emotionless, impervious to appeal, silently shaping the biomass.”

These new digital surveillance and control mechanisms will be no less oppressive for being virtual rather than physical. Contact tracing apps, for example, have proliferated with at least 120 different apps in used in 71 different states, and 60 other digital contact-tracing measures have been used across 38 countries. There is currently no evidence that contact tracing apps or other methods of digital surveillance have helped to slow the spread of covid; but as with so many of our pandemic policies, this does not seem to have deterred their use.

Other advanced technologies were deployed in what one writer has called, with a nod to Orwell, “the stomp reflex,” to describe governments’ propensity to abuse emergency powers. Twenty-two countries used surveillance drones to monitor their populations for covid rule-breakers, others deployed facial recognition technologies, twenty-eight countries used internet censorship and thirteen countries resorted to internet shutdowns to manage populations during covid. A total of thirty-two countries have used militaries or military ordnances to enforce rules, which has included casualties. In Angola, for example, police shot and killed several citizens while imposing a lockdown.

Orwell explored the power of language to shape our thinking, including the power of sloppy or degraded language to distort thought. He articulated these concerns not only in his novels Animal Farm and 1984 but in his classic essay, “Politics and the English Language,” where he argues that “if thought corrupts language, language can also corrupt thought.”

The totalitarian regime depicted in 1984 requires citizens to communicate in Newspeak, a carefully controlled language of simplified grammar and restricted vocabulary designed to limit the individual’s ability to think or articulate subversive concepts such as personal identity, self-expression, and free will. With this bastardization of language, complete thoughts are reduced to simple terms conveying only simplistic meaning.  

Newspeak eliminates the possibility of nuance, rendering impossible consideration and communication of shades of meaning. The Party also intends with Newspeak’s short words to make speech physically automatic and thereby make speech largely unconscious, which further diminishes the possibility of genuinely critical thought.

In the novel, character Syme discusses his editorial work on the latest edition of the Newspeak Dictionary:

By 2050—earlier, probably—all real knowledge of Oldspeak [standard English] will have disappeared. The whole literature of the past will have been destroyed. Chaucer, Shakespeare, Milton, Byron—they’ll exist only in Newspeak versions, not merely changed into something different, but actually contradictory of what they used to be. Even the literature of The Party will change. Even the slogans will change. How could you have a slogan like Freedom is Slavery when the concept of freedom has been abolished? The whole climate of thought will be different. In fact, there will be no thought, as we understand it now. Orthodoxy means not thinking—not needing to think. Orthodoxy is unconsciousness.

Several terms of disparagement were repeatedly deployed during the pandemic, phrases whose only function was to halt the possibility of critical thought. These included, among others, ‘covid denier,’ ‘anti-vax,’ and ‘conspiracy theorist’. Some commentators will doubtless mischaracterize this book, and particularly this chapter, using these and similar terms—ready-made shortcuts that save critics the trouble of reading the book or critically engaging my evidence or arguments.

A brief comment on each of these may be helpful in illustrating how they function.

The first term, ‘covid denier,’ requires little attention. Those who sling this charge at any critic of our pandemic response recklessly equate covid with the Holocaust, which suggests that antisemitism continues to infect discourse on both the right and the left. We need not detain ourselves with more commentary on this phrase.

The epithet ‘anti-vax,’ deployed to characterize anyone who raises questions about the mass vaccination campaign or the safety and efficacy of covid vaccines, functions similarly as a conversation stopper rather than an accurately descriptive label. When people ask me whether I am anti-vax for challenging vaccine mandates I can only respond that the question makes about as much sense to me as the question, “Dr. Kheriaty, are you ‘pro-medication’ or ‘anti-medication’?” The answer is obviously contingent and nuanced: which medication, for which patient or patient population, under what circumstances, and for what indications? There is clearly no such thing as a medication, or a vaccine for that matter, that’s always good for everyone in every circumstance and all the time.

Regarding the term “conspiracy theorist,” Agamben notes that its indiscriminate deployment “demonstrates a surprising historical ignorance.” For anyone familiar with history knows that the stories historians recount retrace and reconstruct the actions of individuals, groups, and factions working in common purpose to achieve their goals using all available means. He mentions three examples from among thousands in the historical record.

In 415 B.C. Alcibiades deployed his influence and money to convince the Athenians to embark on an expedition to Sicily, a venture that turned out disastrously and marked the end of Athenian supremacy. In retaliation, Alcibiades enemies hired false witnesses and conspired against him to condemn him to death. In 1799 Napoleon Bonaparte violated his oath of fidelity to the Republic’s Constitution, overthrowing the directory in a coup, assumed full powers, and ending the Revolution. Days prior, he had met with co-conspirators to fine-tune their strategy against the anticipated opposition of the Council of Five Hundred.

Closer to our own day, he mentions the March on Rome by 25,000 Italian fascists in October 1922. Leading up to this even, Mussolini prepared the march with three collaborators, initiated contacts with the Prime Minister and powerful figures from the business world (some even maintain that Mussolini secretly met with the King to explore possible allegiances). The fascists rehearsed their occupation of Rome by a military occupation of Ancona two months prior.

Countless other examples, from the murder of Julius Caesar to the Bolshevik revolution, will occur to any student of history. In all these cases, individuals gathering in groups or parties to strategize goals and tactics, anticipate obstacles, then act resolutely to achieve their aims. Agamben acknowledges that this does not mean it is always necessary to aver to ‘conspiracies’ to explain historical events. “But anyone who labelled a historical who tried to reconstruct in detail the plots that triggered such events as a ‘conspiracy theorist’ would most definitely be demonstrating their own ignorance, if not idiocy.”

Anyone who mentioned “The Great Reset” in 2019 was accused of buying into a conspiracy theory—that is, until World Economic Forum founder and executive chairman Klaus Schwab published a book in 2020 laying out the WEF agenda with the helpful title,Covid-19: The Great Reset. Following new revelations about the lab leak hypothesis, U.S. funding of gain-of-function research at the Wuhan Institute of Virology, vaccine safety issues willfully suppressed, and coordinated media censorship and government smear campaigns against dissident voices, it seems the only difference between a conspiracy theory and credible news was about six months.

*  *  *

Originally posted at 'Human Flourishing' Substack.

Tyler Durden Mon, 05/16/2022 - 23:45

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Vaccinia virus MacGyvers a makeshift tool to repair its DNA, exposing a vulnerability that could be targeted

Instead of relying on the cell’s repair mechanisms, the vaccinia virus MacGyvers a tool for DNA repair from one that it already uses to copy DNA, reports…

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Instead of relying on the cell’s repair mechanisms, the vaccinia virus MacGyvers a tool for DNA repair from one that it already uses to copy DNA, reports a team of researchers at the Medical University of South Carolina (MUSC) in the Journal of Virology. Blocking that tool – an enzyme known as polymerase – at once disrupts the virus’s ability to copy and to repair DNA, exposing an Achilles’ heel that could be targeted with a therapeutic. 

Credit: Medical University of South Carolina. Photo by Sarah Pack.

Instead of relying on the cell’s repair mechanisms, the vaccinia virus MacGyvers a tool for DNA repair from one that it already uses to copy DNA, reports a team of researchers at the Medical University of South Carolina (MUSC) in the Journal of Virology. Blocking that tool – an enzyme known as polymerase – at once disrupts the virus’s ability to copy and to repair DNA, exposing an Achilles’ heel that could be targeted with a therapeutic. 

“For vaccinia virus, polymerase is a Sawzall – a tool that you can use for everything” said Paula Traktman, Ph.D., senior author of the article and dean of the College of Graduate Studies at MUSC, who has studied the virus for decades. “Viruses have smaller chromosomes, and so they’ve evolved to be able to use their tools for different things.”

“It’s like the virus’s Swiss Army knife,” said Conor Templeton, Ph.D.  lead author of the article, who was a predoctoral candidate in the Traktman laboratory during the study and has since completed his doctorate. “It’s a protein that’s involved in replicating or copying DNA, but it also seems to be involved in repair.”

Such detailed basic science findings about the way viruses copy and repair their DNA have paved the way for breakthrough antiviral therapies in the past 20 years, said Traktman.

“HIV antiretroviral drugs were made by really painstaking analysis of which proteins in the virus are essential, leading to drugs that now have made it a chronic disease,” she said. “A curative treatment for hepatitis C was made possible by painstaking analysis of which proteins are essential for the virus. The more we know about the enemies, the better the weapons we can develop against them.”

Better therapies for pox viruses are certainly needed. The vaccinia virus is a close relative of the virus causing smallpox and was used in the vaccine that successfully eradicated it in the late 20th century. Although smallpox no longer naturally occurs, the threat that it might be used as a bioweapon remains, and currently, there is only one approved antiviral agent against it. Other pox viruses, most notably monkeypox, continue to afflict humans and can be lethal.

Vaccinia is a large DNA virus made up of about 200 genes, and its approach to survival differs markedly from that of smaller, nimbler RNA viruses, such as that which causes COVID-19. The RNA viruses mutate quickly to outrun the body’s immune system. However, they do so at the cost of corrupting their genome. Vaccinia virus prefers a slower, steadier approach and is less likely to make mistakes, helping to ensure genomic stability.

“Vaccinia has gone for ‘I may not be a Ferrari, but I’m a jeep, and I’m going to come out undamaged, and I’m going to be stable, and I’m going to stick around,’” said Traktman.

Unlike other DNA viruses, vaccinia virus does not set up shop in the cell’s nucleus but instead stays in the cytoplasm, where it begins reproducing itself using only the tools it brought with it.

“The nucleus is like the kitchen of the cell,” said Traktman. “If you came into somebody’s house to cook dinner, you would go to their kitchen because that’s where all the necessary equipment is. You wouldn’t decide to go downstairs to their basement because then you’d have to start from scratch. But that’s what vaccinia does. It says ‘I’m not going into the kitchen where you cook. I’m going to just set up shop in the basement, where there’s lots of space. I’ll build everything I need.’”

The MUSC team wanted to see how vaccinia virus would react to damage to its DNA caused by ultraviolet (UV) radiation. They chose UV radiation because it is already known to affect viral replication negatively. They also wanted to know whether exposing the cell to UV radiation one hour before infection with vaccinia would affect the virus’s ability to copy and repair DNA.

The MUSC team found that exposing cells to UV radiation either one hour before or four hours after infection with vaccinia virus reduced the number of mature viral units, or virions, vaccinia was able to produce.

The enzyme polymerase is known to be necessary for successful viral replication, and UV radiation can prevent it from doing its job.

“Polymerase is like a car running down the road,” said Templeton. “It runs smoothly when the road is nice and flat. But UV radiation acts like a speed bump, stopping it in its tracks.”

The UV radiation can cause damage that makes it impossible for DNA replication to continue.

The team found UV-caused damage in the viral DNA of cells irradiated four hours after infection but not in those irradiated an hour before infection. The cells irradiated at four hours after infection also produced 30 times fewer new viruses. This UV-caused damage could account for the reduced infectivity of these cells. Although viral DNA levels were able to recover slightly by 10 to 18 hours, suggesting some viral DNA repair, blocking polymerase resulted in a further tenfold to twentyfold reduction.

“Polymerase is a well-known character in DNA replication,” said Traktman. “It’s a well-known character in actually synthesizing the genome, but this is its debut in repair.”

In essence, the virus’s polymerase “multitasks,” but in so doing makes the virus vulnerable. Because vaccinia relies on polymerase both for DNA copying and repair, blocking it could be a particularly devastating weapon against the virus. The current blocking agent, however, is too broad, and a much more tailored one would be needed for the clinic.

Next, the MUSC team wants to understand better why blocking polymerase makes the DNA more vulnerable to damage and less able to repair itself.

“We want to establish the ensemble of culprits in that process and then try to understand why it is that when you inhibit polymerase function, you see this sensitivity,” said Templeton.

About MUSC

Founded in 1824 in Charleston, MUSC is home to the oldest medical school in the South as well as the state’s only integrated academic health sciences center, with a unique charge to serve the state through education, research and patient care. Each year, MUSC educates and trains more than 3,000 students and nearly 800 residents in six colleges: Dental Medicine, Graduate Studies, Health Professions, Medicine, Nursing and Pharmacy. MUSC brought in more than $327.6 million in biomedical research funds in fiscal year 2021, continuing to lead the state in obtaining federal and National Institutes of Health funding, with more than $220 million. For information on academic programs, visit musc.edu.

As the clinical health system of the Medical University of South Carolina, MUSC Health is dedicated to delivering the highest-quality and safest patient care available while training generations of compassionate, competent health care providers to serve the people of South Carolina and beyond. Patient care is provided at 14 hospitals with approximately 2,500 beds and five additional hospital locations in development, more than 300 telehealth sites and nearly 750 care locations situated in the Lowcountry, Midlands, Pee Dee and Upstate regions of South Carolina. In 2021, for the seventh consecutive year, U.S. News & World Report named MUSC Health the No. 1 hospital in South Carolina. To learn more about clinical patient services, visit muschealth.org.

MUSC and its affiliates have collective annual budgets of $4.4 billion. The more than 24,000 MUSC team members include world-class faculty, physicians, specialty providers, scientists and care team members who deliver groundbreaking education, research, technology and patient care.


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World-first study reveals why people with COPD are more susceptible to COVID-19

Researchers from the Centenary Institute and the University of Technology Sydney have published the first study showing why people with chronic obstructive…

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Researchers from the Centenary Institute and the University of Technology Sydney have published the first study showing why people with chronic obstructive pulmonary disease (COPD) are at higher risk of developing severe COVID-19.

Credit: Centenary Institute

Researchers from the Centenary Institute and the University of Technology Sydney have published the first study showing why people with chronic obstructive pulmonary disease (COPD) are at higher risk of developing severe COVID-19.

The findings, reported in the American Journal of Respiratory and Critical Care Medicine, could lead to the development of new therapeutic interventions that reduce COVID-19 infection in COPD patients.

An inflammatory lung condition, COPD causes airway blockage and makes it difficult to breathe. It affects around 400 million people globally. The increased susceptibility to COVID-19 of COPD patients is still to be fully understood.

In the study, the researchers infected differentiated airway cells from COPD patients and healthy people with SARS-CoV-2 (the virus that causes COVID-19).

The researchers found that the COPD airway cells had 24-fold greater infection with SARS-CoV-2 than the healthy cells.

“We examined the genetic information of infected cells through advanced single cell RNA-sequencing analysis,” said lead author of the study, Dr Matt Johansen, from the Centenary UTS Centre for Inflammation.

“Seven days after SARS-CoV-2 infection, there was a 24-fold increase of viral load in the COPD patient airway cells compared to the cells taken from healthy individuals.”

Significantly, the team found that the infected COPD cells had increased levels of transmembrane protease serine 2 (TMPRSS2) and cathepsin B (CTSB). Both are enzymes that SARS-CoV-2 uses to enter into the host cell.

“These two enzymes are increased in COPD patients and favour greater SARS-CoV-2 infection compared to healthy people. Simply put, easier and increased cell infection makes it far more likely that individuals with COPD will have more severe disease outcomes,” said Dr Johansen.

Other results from the study showed additional reasons for COPD patient susceptibility to severe COVID-19.

Key anti-viral proteins (interferons) that protect against infection were largely blunted in the COPD patient airway cells. This was a likely trigger in causing increased viral production in COPD patients.

Dr Johansen said that infected COPD patient airway cells also had higher levels of pro-inflammatory cytokines, which are linked to more severe COVID-19 and COPD outcomes.

“COPD is an inflammatory disease with patients having increased inflammation at baseline compared to healthy people. It’s highly likely that SARS-CoV-2 exacerbates this existing high inflammation level which leads to even poorer outcomes,” he said.

Initial laboratory drug testing by the researchers, to inhibit the enzymes TMPRSS2 and CTSB, and to target the high inflammation levels, successfully and substantially reduced SARS-CoV-2 viral levels in COPD patient cells, ultimately confirming the study’s results.

“Collectively, these findings have allowed us to understand the mechanisms of increased COVID-19 susceptibility in COPD patients,” said Professor Phil Hansbro, the study’s senior author and Director of the Centenary UTS Centre for Inflammation.

“We believe that new drug treatments targeting relevant enzymes and pro-inflammatory responses in SARS-CoV-2 infection could have excellent therapeutic potential in reducing the severity of COVID-19 in patients with COPD.”

Professor Hansbro said the research was critical with hundreds of millions of people affected by COPD globally and with COVID-19 likely to be around for many years to come.

[ENDS]

Publication:

Increased SARS-CoV-2 Infection, Protease and Inflammatory Responses in COPD Primary Bronchial Epithelial Cells Defined with Single Cell RNA-Sequencing.

https://www.atsjournals.org/doi/10.1164/rccm.202108-1901OC

Images:

Dr Matt Johansen: https://drive.google.com/file/d/1Wc5WxHcS1fSWE68Q7xu8jT53Dki2ZBo4/

 

Professor Phil Hansbro:

https://drive.google.com/file/d/1GaHOyCjXfSb3hsE_bS-g2Cxs81dEhL4G/

 

For all media and interview enquiries, please contact

Tony Crawshaw, Media and Communications Manager, Centenary Institute on 0402 770 403 or email: t.crawshaw@centenary.org.au

 

About the Centenary Institute

The Centenary Institute is a world-leading independent medical research institute, closely affiliated to the University of Sydney and the Royal Prince Alfred Hospital. Our research focuses on three key areas: cancer, inflammation and cardiovascular disease. Our strength lies in uncovering disease mechanisms and applying this knowledge to improve diagnostics and treatments for patients.

For more information about the Centenary Institute, visit centenary.org.au

 

About the University of Technology Sydney (UTS)

The University of Technology Sydney (UTS), located in central Sydney, is one of

Australia’s leading universities of technology. It is known for fusing innovation, creativity

and technology in its teaching and research and for being an industry-focused university.

For more information go to uts.edu.au


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