Culture

New funerary and ritual behaviors of the Neolithic Iberian populations discovered

image: Skull found in the Cueva de la Dehesilla

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Universidad de Sevilla

Experts from the Department of Prehistory and Archaeology of the University of Seville have just published a study in the prestigious journal PLOS ONE on an important archaeological find in the Cueva de la Dehesilla (Cádiz). Specifically, two human skulls and a juvenile goat were discovered along with various archaeological structures and materials from a funerary ritual from the Middle Neolithic period (4800-4000 BC) hitherto unknown in the Iberian Peninsula.

"This finding opens new lines of research and anthropological scenarios, where human and animal sacrifice may have been related to ancestral cults, propitiatory rituals and divine prayers in commemorative festivities," explains US researcher Daniel García Rivero.

The archaeological site located in the Cueva de la Dehesilla consists of two adult human skulls, one male one female, the former being older. The female skull shows a depression in the frontal bone, which probably comes from an incomplete trepanation, as well as cuts in the occipital bone produced by decapitation. In addition, a wall was found separating the human skulls and the skeleton of the goat, on the one hand, from a stone altar with a stele and a hearth, on the other. Finally, several uniquely decorated ceramic vessels, some lithic objects and charred plant remains were discovered in the so-called Locus 2.

"These elements display various characteristics that make it an exceptional archaeological find. The differential treatment of skulls with traumatological evidence along with sacrificed animals, as well as the documented archaeological structures and materials do not match the normative funerary record we were working with until now. This discovery is of great importance not only because of its peculiarity, but also because it constitutes a sealed, intact ritual deposit, which is a great opportunity to gain a more detailed insight into the funerary and ritual behaviours of the Neolithic populations of the Iberian Peninsula", emphasises professor García Rivero.

Neolithic funeral rituals

This work contributes in a particular way to the knowledge of the funerary rituals of the middle part of the 5th millennium before Christ, currently the least well known period of the Neolithic populations of the Iberian Peninsula as a whole. The scarce funerary record from that time shows fundamentally individual burials, with secondary burials being unusual. The sort of context just discovered is really extraordinary. Burials usually occur in areas of habitat, and are mostly associated with remains of ceramics and shells, as well as homes, which reflect the importance of activities related to the use of fire, but without stone structures like those now documented in the mountains of Cádiz.

The study and review of the entire funerary record of this period allows us to offer a kind of cultural mosaic in relation to the funerary and ritual traditions of these peasant and herding populations, with a probable division between the Andalusian region and the eastern seaboard of the peninsula, the two regions where most data is available today.

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University of Seville

Potential drug target for dangerous E. coli infections identified

image: The spider-like icosahedral shape is an abstract depiction of the Shiga toxin bacteriophage with a red genome, stylised as the puppet master of a potentially deadly EHEC infection.

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UNSW Sydney

Escherichia coli, known as E. coli, are bacteria which many people associate with causing mild food poisoning, but some types of E. coli can be fatal.

UNSW Science microbiologists studied an E. coli strain that causes a severe intestinal infection in humans: enterohemorrhagic E. coli (EHEC). Their findings were published this week in the journal PNAS (Proceedings of the National Academy of Sciences).

EHEC is a food-borne pathogen that releases Shiga toxins during infection, resulting in kidney and neurological damage.

Dr Jai Tree, the study's senior author, said the researchers' discovery of a new molecular pathway that controls Shiga toxin production was important because there was no commercially available treatment for EHEC infections.

"Antibiotic treatment of these infections is generally not recommended because antibiotics stimulate production of the Shiga toxin, leading to an increased risk of kidney failure, neurological damage, and death," Dr Tree said.

"The new pathway that we have found reduces toxin production and is not expected to be stimulated by antibiotic treatment. So, our results identify a potential new target for the development of drugs that can suppress Shiga toxin production during EHEC infection.

"It's still early days, however, and we need to conduct a lot more research to understand if our findings apply to a broad range of clinical EHEC isolates and to both types of Shiga toxins produced by human EHEC isolates."

How EHEC infections start

Dr Tree said there were several ways in which people could become infected with EHEC.

"EHEC is mainly found in the faeces of cows and sheep and people can become infected through contact with farm animals and their faeces, or via person-to-person infection if people come into contact with tiny amounts of faeces from a sick person - for example, directly or indirectly by touching contaminated surfaces," he said.

"This strain of E. coli can also spread through ingesting the bacteria by eating undercooked minced meat (for example, in hamburgers), eating contaminated fresh produce like salad vegetables, or drinking contaminated water or unpasteurised milk.

"Children under five years old and older people are at greatest risk of developing an EHEC infection."

EHEC outbreaks less common but deadly

Dr Tree said while the prevalence of EHEC was low compared to other foodborne pathogens, the disease could be very severe or even fatal. EHEC is a type of STEC (Shiga toxin-producing Escherichia coli).

"EHEC outbreaks occur sporadically in Australia and worldwide. The most significant outbreak occurred in South Australia in 1995 and was caused by contaminated mettwurst, a semi-dry fermented sausage made from raw minced pork preserved by curing and smoking," he said.

"In that outbreak, 143 people were infected - 23 of them suffered kidney and neurological damage. Many of these severe cases were in infants who suffered permanent kidney damage and later required kidney transplants.

"A four-year-old girl suffered multiple strokes and died three days after admission to hospital. This episode triggered a major food safety investigation and outbreaks since 1995 have been smaller."

Dr Tree said globally, Shiga toxin-producing E. coli was still a major food safety concern after a large outbreak in Germany in 2011.

"The strain in Germany was spread mostly via consumption of contaminated sprouts and in several cases, from close contact with an infected person," he said.

"During this outbreak more than 4000 people were infected and 50 people died."

New pathway 'hiding in plain sight'

Dr Tree said the UNSW research was the first discovery of a new pathway that controls the Shiga toxins in almost 20 years.

"In 2001, researchers at Tufts and Harvard universities first showed how production of the Shiga toxin was controlled by a bacterial virus, known as a bacteriophage, within the genome. This has been the only known pathway that controls Shiga toxin production for almost two decades," he said.

"We have extended that work to show a new mechanism of toxin control that is, surprisingly, buried within the start of the DNA sequence that encodes the Shiga-toxin messenger RNA - a working copy of the gene.

"We discovered a very short piece of the toxin messenger RNA is made into a regulatory non-coding RNA that silences the toxin and promotes growth of the pathogen."

Dr Tree said their findings were a surprise because Shiga toxin genes have been well studied, with almost 7000 published studies in the past 40 years.

"Only recently have we been able use advances in RNA sequencing technology to detect the presence of the new regulatory non-coding RNA embedded within the Shiga toxin messenger RNA," he said.

"This new regulatory non-coding RNA had been hiding in plain sight for almost 20 years."

Implications for treating EHEC infections

Dr Tree said the researchers' findings opened up new possibilities for the treatment of EHEC infections.

"Patients largely receive supportive care to manage disease symptoms and to reduce the effects of the toxin on the kidneys," he said.

"Our work shows a new mechanism for controlling toxin production that may be amenable to new RNA-based therapeutics to inhibit toxin production during an infection. We anticipate this would expand intervention options and potentially allow use of antibiotics that are currently not recommended because they stimulate Shiga toxin production.

"New treatments could therefore reduce the risk of kidney damage, neurological complications and death. We look forward to testing these new interventions in the next stage of our research."

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University of New South Wales

Low level alcohol use during pregnancy can impact child's brain development

New research from the University of Sydney finds that even low levels of alcohol consumption during pregnancy can have an impact on a child's brain development and is associated with greater psychological and behavioural problems in youth including anxiety, depression and poor attention.

Published today in the prestigious American Journal of Psychiatry, the study was led by the University's Matilda Centre for Research in Mental Health and Substance Use.

The impact of low-level alcohol use during pregnancy on child development is relatively unknown and there has been extensive debate about whether there is a safe level of consumption.

The researchers investigated whether any alcohol consumption in pregnancy was related to psychological, behavioural, neural and cognitive differences in children aged nine to ten years. With a sample of 9,719 youth, this is the largest study to investigate the impacts of low-level alcohol use during pregnancy. Low levels of drinking were considered one to two drinks per occasion with maximum of six drinks per week.

"Our research found that even small amounts of alcohol consumed while pregnant can have a significant impact on a child's brain development," said lead author Ms Briana Lees, PhD candidate at the Matilda Centre.

"Previous research has shown that very heavy alcohol use, such as binge drinking, during pregnancy can cause harm to the baby. However, this study shows that any alcohol use during pregnancy, even low levels, is associated with subtle, yet significant behavioural and psychological effects in children including anxiety, depression and poor attention.

"This study is so important because in Australia, around 50 percent of women drink alcohol before they know they are pregnant, and 25 percent do so after they know. The vast majority consume one or two standard drinks per occasion which this study shows is enough to impact the baby's brain."

Study findings

In the study, 25 percent of children had been exposed to alcohol in utero (in the womb), 60 percent of these children had been exposed to low-level alcohol use, and 40 per cent had been exposed to heavier levels. Heavier exposure being three or more drinks per occasion or seven or more drinks per week.

Children who were exposed to low levels of alcohol in-utero at any time during pregnancy experienced more psychological/emotional problems (including anxiety, depression and being withdrawn) and behavioural problems (including poor attention and being impulsive) than unexposed children.
There was a 25 percent increased likelihood of an attention deficit hyperactivity disorder (ADHD) diagnosis in children who were exposed to slightly heavier levels of alcohol (approximately 36 drinks) in the first 6-7 weeks of pregnancy.
Heavier alcohol use during early pregnancy was also associated with rule breaking behaviour and aggression, with a 30 percent higher risk of the child being diagnosed with oppositional defiant disorder than unexposed youth.

There were differences observed in brain volume and surface area among the exposed children which contributed to the psychological and behavioural problems.
The estimated number of drinks consumed during pregnancy ranged from 0-90 with the average being 27. The majority of drinks were consumed in the first 6-7 weeks prior to pregnancy knowledge.

"Generally, the more a child was exposed to alcohol in utero the more severe the outcomes were," said Ms Lees.

"Children experienced negative effects even if they were only exposed to low levels of alcohol during very early pregnancy (approximately 16 drinks in the first six to seven weeks) and then the mother stopped drinking. The difficulty is many women don't know they are pregnant at that early stage.

Senior author Professor Maree Teesson, Director of the Matilda Centre said these findings are important for families, clinicians and policy makers moving forward.

"This research highlights the importance for women to be aware of the effects that even low levels of drinking can have on the brain development of babies," she said.

"The safest option during pregnancy is to abstain from drinking any alcohol.

"This information is also important for women planning pregnancies. Even when planning pregnancy, it is safer to abstain from any drinking. Any alcohol consumption from conception throughout the entire pregnancy can impact the brain development of their baby."

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University of Sydney

Astronomers model, determine how disk galaxies evolve so smoothly

image: This illustration shows how two sample star orbits are scattered from nearly circular orbits by the gravity of massive clumps within galaxies. Researchers have found that millions of orbital changes, like those shown here, smooth the overall light profile of galaxy disks. The blue star is scattered several times. The orange star is captured by the gravity of a clump and moves around it. A typical, relatively smooth spiral galaxy (UGC 12224) is shown in the background.

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Illustration by Jian Wu/Iowa State University. Galaxy image from the Sloan Digital Sky Survey.

AMES, Iowa - Computer simulations are showing astrophysicists how massive clumps of gas within galaxies scatter some stars from their orbits, eventually creating the smooth, exponential fade in the brightness of many galaxy disks.

Researchers from Iowa State University, the University of Wisconsin-Madison and IBM Research have advanced studies they started nearly 10 years ago. They originally focused on how massive clumps in young galaxies affect star orbits and create galaxy disks featuring bright centers fading to dark edges.

(As Curtis Struck, an Iowa State professor of physics and astronomy, wrote in a 2013 research summary: "In galaxy disks, the scars of a rough childhood, and adolescent blemishes, all smooth away with time.")

Now, the group has co-authored a new paper that says their ideas about the formation of exponential disks apply to more than young galaxies. It's also a process that is robust and universal in all kinds of galaxies. The exponential disks, after all, are common in spiral galaxies, dwarf elliptical galaxies and some irregular galaxies.

How can astrophysicists explain that?

By using realistic models to track star scattering within galaxies, "We feel we have a much deeper understanding of the physical processes that resolve this almost-50-year-old key problem," Struck said.

Gravitational impulses from massive clumps alter the orbits of stars, the researchers found. As a result, the overall star distribution of the disk changes, and the exponential brightness profile is a reflection of that new stellar distribution.

The astrophysicists' findings are reported in a paper just published online by the Monthly Notices of the Royal Astronomical Society. Co-authors are Struck; Jian Wu, an Iowa State doctoral student in physics and astronomy; Elena D'Onghia, an associate professor of astronomy at Wisconsin; and Bruce Elmegreen, a research scientist at IBM's Thomas J. Watson Research Center in Yorktown Heights, New York.

Stars are scattered, disks are smoothed

The latest computer modeling - led by Wu - is a capstone topping years of model improvements, Struck said. Previous models treated the gravitational forces of galaxy components more approximately, and researchers studied fewer cases.

The latest models show how star clusters and clumps of interstellar gases within galaxies can change the orbits of nearby stars. Some star-scattering events significantly change star orbits, even catching some stars in loops around massive clumps before they can escape to the general flow of a galaxy disk. Many other scattering events are less powerful, with fewer stars scattered and orbits remaining more circular.

"The nature of the scattering is far more complex than we previously understood," Struck said. "Despite all this complexity on small scales, it still averages out to the smooth light distribution on large scales."

The models also say something about the time it takes for these exponential galaxy disks to form, according to the researchers' paper. The types of clumps and initial densities of the disks affect the speed of the evolution, but not the final smoothness in brightness.

Speed in this case is a relative term because the timescales for these processes are billions of years.

Over all those years, and even with model galaxies where stars are initially distributed in a variety of ways, Wu said the models show the ubiquity of the star-scattering-to-exponential-falloff process.

"Stellar scattering is very general and universal," he said. "It works to explain the formation of exponential disks in so many cases."

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Iowa State University

Education: an influencing factor for intergenerational mobility in Canada

Quebec and Montreal, September 25, 2020 - The relationship between the income levels of parents and their children once they reach adulthood is complex, but education could be one of the factors that influence Canadian intergenerational mobility. This according to a study recently published by INRS (Institut national de la recherche scientifique) professor Xavier St-Denis and Statistics Canada researcher Gaëlle Simard Duplain in Canadian Public Policy/Analyse de politiques. The study looks at the role education levels play in intergenerational income mobility in Canada.

Most studies available on the subject present results based on national or regional income mobility, which can be used to make geographic and historical comparisons. "The underlying mechanisms at play in the relationship between the income of parents and the income of their children, including their education levels and job characteristics, hasn't been studied much in Canada," explained Professor St-Denis.

To measure the effects of education on intergenerational mobility in Canada, the two researchers looked at the data from Statistics Canada's Longitudinal and International Study of Adults (LISA), which covers the period from 1982 to 2014. "Our study shows that in Canada, a child's education level explains 40.5% to 50.1% of the correlation between a child's income once they reach adulthood and their parent's income," said Professor St-Denis. "That's similar to the results observed in the United States and the UK."

Income inequality repeated from one generation to the next

According to the research results, social and economic inequalities occur early in life and have long-lasting effects.

The results also point to the existence of differentiation mechanisms that operate throughout the working lives of people with similar levels of education. "Intergenerational mobility partly results from the different characteristics in a child's environment, from their cumulative and complementary effects. It also results from the time, financial resources, and social capital that parents with a higher income are more likely to invest in their children's education," said Professor St-Denis, who recently joined INRS's Urbanisation Culture Société Research Centre.

If the income of people living in a society is only marginally dependent on their parents' income, that society is said to have a high degree of intergenerational mobility. In other words, the context in which children grow and evolve does not depend solely on their parents' economic situation. Access to education, for example, could depend not on parents' ability to pay for it, but on the child's interest in pursuing their studies.

Inversely, when the income of individuals in adulthood is, on average, similar to that of their parents, inequalities are reproduced to a much greater degree from one generation to the next. This can result in intergenerational income immobility.

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Institut national de la recherche scientifique - INRS

Ultrapotent antibody mix blocks COVID-19 virus attachment

image: Pandemic coronavirus researchers David Vessler (left) and Alejandra Tortorici (right) at the University of Washington School of Medicine in Seattle. The Veesler lab uses cryo-electron microscopy to study the structure and function of the coronavirus' infectivity machinery, and how neutralizing antibodies can lock down this machinery and block the virus from attaching to and fusing with host cells.

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Matthew McCallum/Veesler Lab

A mix of ultrapotent antibodies from recovered COVID-19 patients has been shown to recognize and lock down the infection machinery of the pandemic coronavirus and keep it from entering cells. Each of the antibody types performs these overlapping tasks slightly differently.

Low doses of these antibodies, individually or as a cocktail, were also shown to protect hamsters from infection when exposed to the coronavirus by preventing it from replicating in their lungs.

An advantage of such cocktails is that they might also prevent the natural mutant forms of the virus that arose during this pandemic to escape treatment. As some variants in the infection machinery have already been discovered during the coronavirus pandemic, using a mix of antibodies allows for neutralization of a broad spectrum of such viral variants.

In addition to preventing virus entry into host cells, the presence of the antibodies also seems to set off the infection-fighting actions of other immune cells, which arrive to clear out the virus.

"We believe that leveraging multiple, distinct, complementary mechanisms of action could provide additional benefits for clinical applications," the researchers noted.

The researchers determined how the antibodies worked on a molecular level through cryo-electron microscopy studies of the resulting changes in the configuration of the virus infection machinery. Besides directly preventing interactions with the host receptor, one of the two discovered antibodies locks the infection machinery in an inactive conformation, meaning it could not fuse with the host membrane on the surface of the cell. If unable to fuse, the coronavirus cannot break in and deliver its RNA to commandeer the cell.

The findings of this research are reported Sept. 24 in a rapid release paper in Science. Here is the paper.

The senior authors were Dr. Katja Fink of Vir Biotechnology and Dr. David Veesler, associate professor of biochemistry at the University of Washington School of Medicine. Veesler has studied the molecular structure and infection mechanisms of a variety of coronaviruses and other viruses.

The lead authors were M. Alejandra Tortorici of the UW Department of Biochemistry and the Institut Pasteur in Paris, and Martina Beltramello of Humab BioMed, a subsidiary of Vir Biotechnology in Switzerland. Researchers from Washington University in St Louis, Rega Institute in Belgium, the University of Milan, Italy, and the University of Texas in Dallas also collaborated on the research.

Efficient therapeutic options are needed to control the spread of SARS-CoV-2 that has caused more than 978,000 fatalities worldwide. While the world awaits approved vaccines, pharmaceuticals to prevent or treat infections from the pandemic coronavirus are being sought that might be quicker to develop and test. These might both address the gap until vaccines are widely distributed, and still be needed for use after vaccines are available.

"Our results pave the way to implement antibody cocktails for prophylaxis or therapy that might have the advantage of circumventing or limiting the emergence of viral escape mutants," the researchers noted. The antibody cocktail in their study needs to undergo trials in humans to determine safety and effectiveness.

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University of Washington School of Medicine/UW Medicine

Scholars untangle marketing's complex role in understanding political activities

As 2020 began, many pundits predicted a politically charged year, but few predicted that it would include a global pandemic overtaxing healthcare resources, strained U.S. race relations resulting in mass demonstrations across the globe, devastating fires consuming massive swaths of the United States, and a catastrophic global economic downturn. This month's special issue of the Journal of Public Policy & Marketing acknowledges the role that marketing does and can play in addressing political activities with articles that explore key topics like elections, voting, corporate political advocacy, and consumer political identities. Two commentaries from an industry veteran and an esteemed journal editor offer both applied and scholarly paths for future marketing strategies and research. While the articles were not intended to respond directly to the specific events, they still provide theories explaining firm, consumer, agency, and other stakeholder behaviors along with strategy implications.

"A Vote of Competence: How a Similar Upbringing to Political Candidates Influences Voting Choice," by Matthew D. Meng and Alexander Davidson

The authors explore a commonly used political strategy: showing how similar political candidates are to constituents and voters. The authors confirm this relationship but expand the understanding as it relates to a candidate's competence along with particular audiences for whom the strategy is most effective.

https://doi.org/10.1177/0743915620943181

"Citizen Participation in Political Markets: Extending Service-Dominant Logic to Public Policy," by Mark Peterson and Robert W. Godby

The results of this study suggest that the decisions offered by citizens in a research setting reflect citizens' competence for informing elected representatives and policy makers regarding budgeting. When constituents can be brought into the process of ongoing governance in an effective and manageable fashion that does not require an expensive referendum or election, distortions of democracy will be reduced.

https://doi.org/10.1177/0743915620912287

"To Change the Law, Defy the Law: Hijacking the Cause and Co-Opting Its Advocate," by Bernard Cova

This research examines how the advocates of a cause respond to corporate approaches that integrate marketing and political activities for the cause. The findings reveal that such marketing activities resemble co-optation of the initial advocate of the cause and hijacking of the cause they advocate for.

https://doi.org/10.1177/0743915620943855

"Brands Taking a Stand: Authentic Brand Activism or Woke Washing?" by Jessica Vredenburg, Sommer Kapitan, Amanda Spry, and Joya A. Kemper

The authors draw on theory to determine how and when a brand engaging with a sociopolitical cause can be viewed as authentic, finding that moderate, optimal incongruence between brand and cause acts as a boundary condition. They explore important policy and practice implications for current and aspiring brand activists, from specific brand-level standards in marketing efforts to third-party certifications and public sector partnerships.

https://doi.org/10.1177/0743915620947359

"The Activist Company: Examining a Company's Pursuit of Societal Change Through Corporate Activism Using an Institutional Theoretical Lens," by Meike Eilert and Abigail Nappier Cherup

Using institutional theory, the authors create a framework showing how corporate activism can address these societal problems through influence and change strategies that can target the institutional environment "top-down" or "bottom-up." This framework further investigates how the company's identity orientation facilitates corporate activism.

https://doi.org/10.1177/0743915620947408

"Political Ideology in Consumer Resistance: Analyzing Far-Right Opposition to Multicultural Marketing," by Sofia Ulver and Christofer Laurell

The authors explore the discursive efforts in far-right consumer resistance to advance a political agenda through protests directed at brands' multicultural advertising and analyze how these consumers conceptualize their adversaries in the marketplace. In contrast to previous framings of adversaries identified in consumer research, where resistance is typically anticapitalist and directed toward firms' unethical conduct or the exploitation by the global market economy per se, the authors find that the following discursive themes stand out in the far-right consumer resistance: the emphasis on the state as main antagonist, the indifference to capitalism as a potential adversary, and overt contestation of liberal ethics.

https://doi.org/10.1177/0743915620947083

"Politics at the Mall: The Moral Foundations of Boycotts," by Daniel Fernandes

This article demonstrates that although both liberals and conservatives engage in consumer political actions, they do so for different reasons influenced by their unique moral concerns: Liberals engage in boycotts and buycotts that are associated with the protection of harm and fairness moral values (individualizing moral values), whereas conservatives engage in boycotts and buycotts that are associated with the protection of authority, loyalty, and purity moral values (binding moral values). In addition, the individualizing moral values lead to a generally more positive attitude toward boycotts, which explains why liberals are more likely to boycott and buycott.

https://doi.org/10.1177/0743915620943178

"Commentary: Brand Activism in a Political World," by Christine Moorman

The Editor in Chief of the venerable Journal of Marketing and author of "The CMO Survey" analyzes CMO's changing opinions on firm activism.

https://doi.org/10.1177/0743915620945260

"Commentary: Patagonia and the Business of Activism," by Vincent Stanley

Patagonia's Director of Philosophy discusses the brand's decision to take public stands on critical issues such as climate change.

https://doi.org/10.1177/0743915620943181

For the full issue and contact information, visit https://journals.sagepub.com/toc/ppoa/39/4.

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American Marketing Association

3D printed nasal swabs work as well as commercial swabs for COVID-19 diagnostic testing

image: First author Summer Decker, PhD, directs the USF Health Radiology-Tampa General Hospital Division of 3D Clinical Applications, which creates and prints 3D anatomical models for surgeons and other clinicians and designs medical devices.

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© USF Health|University of South Florida

TAMPA, Fla. (Sept. 25, 2020) - As COVID-19 quickly spread worldwide this spring, shortages of supplies, including the nasopharyngeal (nasal) swabs used to collect viral samples, limited diagnostic testing.

Now, a multisite clinical trial led by the University of South Florida Health (USF Health) Morsani College of Medicine and its primary hospital affiliate Tampa General Hospital (TGH) provides the first evidence that 3D-printed alternative nasal swabs work as well, and safely, as the standard synthetic flocked nasal swabs.

The results were published online Sept. 10 in Clinical Infectious Diseases. A commentary accompanying the paper cites the authors' timely, collaborative response to supply chain disruptions affecting testing capacity early in the pandemic.

Seeking a solution to an unprecedented demand for nasal swabs at their own institution and others, USF Health researchers in the Departments of Radiology and Infectious Diseases reached out to colleagues at TGH; Northwell Health, New York's largest health care provider; and leading 3D-printer manufacturer Formlabs. Working around the clock, this multidisciplinary team rapidly designed, tested and produced a 3D printed nasal swab prototype as a replacement for commercially-made flocked nasal swabs. Bench testing (24-hour, 3-day, and leeching) using respiratory syncytial virus as a proxy for SARS-CoV-2, as well as local clinical validation of the final prototype (fabricated with FDA-approved nontoxic, surgical grade materials), was successfully completed in mid-March 2020.

The larger-scale clinical trial began in late March at three sites: TGH, Northwell Health, and Philadelphia-based Thomas Jefferson University Hospital. (Other sites joined later.)

Although USF Health held a provisional patent on the concept and design of the new 3D printed swab, they freely shared the information with hospitals, clinics, governments and international agencies experiencing supply chain shortages. Since the first batches of 3D printed swabs were processed, tens of millions of the USF Health-invented devices have been used in 22 countries, said lead author Summer Decker, PhD, an associate professor of radiology at the USF Health Morsani College of Medicine. Dr. Decker directs the USF Health Radiology-TGH Division of 3D Clinical Applications, a group with expertise in creating and printing 3D anatomical models for surgeons and other clinicians as well as designing medical devices.

"In the midst of a pandemic, our team of experts representing academic medicine, health care delivery systems, and the medical device industry put aside boundaries to quickly work together toward a common purpose," Dr. Decker said. "It's rewarding that the novel design for a 3D swab we created has been adopted around the world, equipping more providers to diagnose COVID-19 and hopefully help prevent its spread."

The gold standard for diagnosing respiratory infections is to look for viral genetic material found in mucosal fluid collected with a long, slender swab inserted into the patient's nose and back of the throat. The nasal swab is put into a plastic tube with chemicals that stabilize the sample until the virus-specific genetic material can be extracted and amplified by polymerase chain reaction (PCR) in a diagnostics laboratory. Conventional swabs feature a bushy tip coated with nylon flock; the USF Health doctors designed a tip with a 3D printed textured pattern able to capture a sufficient sample for COVID testing while keeping patient safety and comfort in mind.

The clinical trial fully tested the safety and effectiveness of this 3D printed swab in 291 symptomatic adults undergoing COVID-19 screening at the TGH, Northwell Health and Thomas Jefferson University Hospital sites. The 3D printed nasal swab was compared to the standard synthetic nasal swab across three SARS-CoV-2 testing platforms FDA-authorized for emergency use -- a modified version of the Center for Disease Control and Prevention's real-time reverse transcriptase PCR diagnostic panel, and two commercial molecular diagnostic tests.

"This trial provided the first rigorous head-to-head comparison to make sure that the 3D swab performed as well as the standard," said principal investigator Kami Kim, MD, professor and division director for infectious disease at the USF Health Morsani College of Medicine. "Across all three platforms used in our study, we demonstrated that the commercial swab and the 3D printed swab were comparable for accurate detection of COVID-19 infection."

For both swabs, the only adverse patient reaction documented during the trial was a few instances of slight nasal bleeding. The cost of materials per 3D printed nasal swab ranges from 26-to 46-cents, while commercial swabs cost about $1 each, the authors reported.

Given the ongoing need for widespread COVID-19 testing, the study authors concluded that 3D printing technology offers a viable, cost-efficient option to address swab supply shortages, particularly when local hospitals or other clinical sites already have 3D printing labs equipped to print and process the devices.

Frank Rybicki, MD, PhD, vice chair of operations and quality at the University of Cincinnati College of Medicine's Department of Radiology, wrote a commentary on 3D printing in medicine to accompany the Clinical Infectious Diseases paper. The article frames the contributions of Decker et. al. in the context of the larger 3D manufacturing community.

"Among all parts 3D printed during COVID-19, nasopharyngeal swabs have received the most attention, with participants ranging from humanitarians to charlatans," Dr. Rybicki wrote in his summary. "The authors should be congratulated for staying on the right side of the curve, and for their perseverance, leadership, scientific rigor, and good will."

Credit: 
University of South Florida (USF Health)

RAP tag: A new protein purification approach

Tskuba, Japan - Whether it's our diets, building strength, or as part of medical advancements, it is no secret that proteins form an important part of our lives. Tracking how proteins work and move in cells, and purifying engineered proteins, are important tools for researchers. Traditional approaches to label proteins of interest, called "tagging," have the disadvantage of interfering with protein characteristics, including function and localization. Sometimes, these tags can also cross-react, which makes the information they provide nonspecific. A successful protein tagging system needs to be highly specific and have high affinity.

In a study published in September 2020 in Frontiers in Plant Science, researchers from the University of Tsukuba, led by Professor Kenji Miura, have described a new tagging system for detecting and purifying proteins in plant cells. This approach uses a short sequence called a "RAP tag" to label proteins. An antibody, PMab-2, is then able to specifically recognize the RAP tag and can be used to purify the proteins of interest.

In describing this approach, Professor Miura says, "The high affinity and specificity of immunoaffinity chromatography using monoclonal antibodies makes it a very powerful tool, especially for the purification of proteins expressed at low levels." A hurdle to applying this approach, however, is the high cost of reagents, especially that of antibodies.

To get around this, Professor Miura and colleagues explored whether they could produce the PMab-2 antibody in the plant model Nicotiana benthamiana, a relative of the tobacco plant. Not only could they successfully produce PMab-2, they went on to show that the plant-produced PMab-2 behaved similarly to that produced in animal cells. This discovery opens the door to reducing the cost of antibody production, and could be applied more widely across scientific fields.

Testing the feasibility of a RAP-tagged/ PMab-2 affinity purification approach, the researchers then expressed RAP-tagged proteins in plant cells. They found that these tagged proteins could be specifically identified using the PMab-2 antibody. Moreover, RAP-tagged recombinant proteins, involving the fusion of sequences from more than one protein, and protein complexes were also expressed in these cells and identified by PMab-2. These proteins could also be purified from plant cells using the PMab-2 antibody, indicating that the RAP tag can be used for both protein detection and purification from soluble plant extracts.

"Plants are an extremely valuable resource for molecular biology," explains Professor Miura. "They can be used as bioreactors to produce large amounts of proteins because they are unlikely to suffer from contamination issues faced by bacterial and mammalian cell systems."

The results presented by the team show that this approach has the potential to be widely applied across the molecular sciences.

Credit: 
University of Tsukuba

Spin clean-up method brings practical quantum computers closer to reality

image: If the measurement outcome in the quantum circuit is the |0⦒ state, the spin contaminated wave function |ψCont⦒ is projected out onto the spin annihilated one |ψAnni⦒. The rightmost part of the top line denotes the measurement.

Image: 
Kenji Sugisaki, Kazunobu Sato and Takeji Takui, Osaka City University

Osaka, Japan. Quantum computers are the new frontier in advanced research technology, with potential applications such as performing critical calculations, protecting financial assets, or predicting molecular behavior in pharmaceuticals. Researchers from Osaka City University have now solved a major problem hindering large-scale quantum computers from practical use: precise and accurate predictions of atomic and molecular behavior.

They published their method to remove extraneous information from quantum chemical calculations on Sept. 17 as an advanced online article in Physical Chemistry Chemical Physics, a journal of the Royal Society of Chemistry.

"One of the most anticipated applications of quantum computers is electronic structure simulations of atoms and molecules," said paper authors Kenji Sugisaki, Lecturer and Takeji Takui, Professor Emeritus in the Department of Chemistry and Molecular Materials Science in Osaka City University's Graduate School of Science.

Quantum chemical calculations are ubiquitous across scientific disciplines, including pharmaceutical therapy development and materials research. All of the calculations are based on solving physicist Erwin Schrödinger's equation, which uses electronic and molecular interactions that result in a particular property to describe the state of a quantum-mechanical system.

"Schrödinger equations govern any behavior of electrons in molecules, including all chemical properties of molecules and materials, including chemical reactions," Sugisaki and Takui said.

On classical computers, such precise equations would take exponential time. On quantum computers, this precision is possible in realistic time, but it requires "cleaning" during the calculations to obtain the true nature of the system, according to them.

A quantum system at a specific moment in time, known as a wave function, has a property described as spin, which is the total of the spin of each electron in the system. Due to hardware faults or mathematical errors, there may be incorrect spins informing the system's spin calculation. To remove these 'spin contaminants,' the researchers implemented an algorithm that allows them to select the desired spin quantum number. This purifies the spin, removing contaminants during each calculation--a first on quantum computers, according to them.

"Quantum chemical calculations based on exactly solving Schrödinger equations for any behavior of atoms and molecules can afford predictions of their physical-chemical properties and complete interpretations on chemical reactions and processes," they said, noting that this is not possible with currently available classical computers and algorithms. "The present paper has given a solution by implementing a quantum algorithm on quantum computers."

The researchers next plan to develop and implement algorithms designed to determine the state of electrons in molecules with the same accuracy for both excited- or ground-state electrons.

Credit: 
Osaka City University

A genetic variant that protects against Alzheimer's disease promotes immune cell functions

A new study conducted by researchers at the University of Eastern Finland found that the PLCG2-P522R genetic variant, which protects against Alzheimer's disease, enhances several key functions of immune cells. The results obtained in the study highlight the importance of immune cells as a target of future development of new therapies for Alzheimer's disease.

Alzheimer's disease is the most common form of dementia with more than 40 million affected people worldwide. To this day, there are no existing therapies for the effective prevention or treatment of the disease. Many recently identified Alzheimer's disease-associated risk genes are expressed preferentially or exclusively in microglia, the immune cells of the brain. A study conducted in collaboration with the University of Eastern Finland and the German DZNE institute investigated the role of the microglia-specific Plcg2-P522R genetic variant in Alzheimer's disease and found that it enhances several immune cell-specific functions. The results were published in the Molecular Neurodegeneration journal.

A genome-wide association study from 2017, which included a Finnish cohort of Alzheimer's disease patients and healthy controls, identified Alzheimer's disease-associated risk loci in three genes, TREM2, ABI3 and PLCG2, which are mainly expressed in microglia. Several genetic variants of the TREM2 gene have been found to increase the risk for Alzheimer's disease. These TREM2 variants lead to a partial loss of function of the receptor and impair the activation of microglia. Consequently, the removal of β-amyloid, which accumulates in the brain during Alzheimer´s disease, is reduced. Recently, it has been shown that the phospholipase C gamma 2 (PLCγ2) enzyme is involved in the signaling pathway initiated by TREM2. The PLCG2-P522R variant reduces the risk of developing Alzheimer's disease, but its effects on immune cell functions have not been previously described.

"It is interesting how several Alzheimer's disease-associated risk genes affect microglial cell functions through the same signaling pathway. It shows that targeting this pathway and the cellular functions it regulates may have significant therapeutic potential in the future," says Postdoctoral Researcher Mari Takalo from the Institute of Biomedicine of the University of Eastern Finland.

Protective variant sensitizes and activates immune cells

For this study, a mouse model carrying the Plcg2-P522R genetic variant was developed using the CRISPR-Cas9 gene editing technique in collaboration with the research group of German Professor Christian Haass at the DZNE Institute. The researchers found that the Plcg2-P522R variant increases PLCγ2 enzyme activity and enhances cell viability, phagocytic activity, and immune response in peripheral macrophages as well as in microglia-like cells. The results are in line with a recently published study in which deletion of the PLCG2 gene in microglial cells produced from human-induced stem cells had opposite effects.

"It is intriguing that results generated from cells of different origins that have been exposed to different methods of genetic modification, all point in a similar direction. Although this is just the beginning of research related to the role of PLCγ2 in the context of Alzheimer's disease, these results encourage to continue with further studies," Early Stage Researcher Rebekka Wittrahm says.

The study also looked at the effects of the protective Plcg2-P522R variant in the brain of mice. The changes observed in both the RNA expression analysis and the PET imaging study measuring microglial cell activity suggest increased microglial cell activity in Plcg2-P522R mice.

"Microglial cells with the protective genetic modification seem to be more sensitive to various environmental stimuli and thus, may become more efficient at removing material harmful to the brain, such as β-amyloid. Further research is needed to find out exactly how sensitized microglial cells react in the presence of Alzheimer's disease-related changes in the aging brain," Takalo sums up.

"It is pivotal that we are able to study the role of genes associated with Alzheimer's disease comprehensively at the University of Eastern Finland, from the identification of the risk gene to further functional studies in animal models and patient cohorts," says Professor Mikko Hiltunen, who spearheads the research group.

Credit: 
University of Eastern Finland

How to better understand what makes a virus win during transmission?

The framework, published in Frontiers in Microbiology, was applied on transmission data of the influenza virus, and offers to be a new tool for anticipating the consequences of microbial diversity and optimizing disease control measures.

Estimating fitness variation among microorganisms, meaning their aptitude to survive and reproduce in given conditions, allows to predict their infection trajectories in single hosts and transmission in host populations. Among two viral strains, which will be the one to win against the host's immune response, or upon administration of drugs and vaccines? In virus dynamics, understanding in detail such scenarios is crucial, given the increase in resistance to antivirals and other evolutionary changes. Nowadays, this understanding is enhanced via mathematical models, but the majority of current approaches describe limited scenarios, focusing on competitive exclusion, where one strain of the virus always wins over another because it has higher fitness.

The Mathematical Modelling of Biological Processes research group from Instituto Gulbenkian de Ciência developed a mathematical framework that enables extension beyond such limitation. Based on the Lotka-Volterra model, widely used in ecology, the researchers propose a framework that allows, in addition, verification of scenarios of frequency-dependent competition between microbial strains in a host leading up to transmission. "We applied this framework to a dataset obtained from previous studies, where they estimated different parameters related to differences in transmission fitness between two influenza virus strains in ferrets", explains Erida Gjini, lead author of the study. "We went further and, by considering more complex interactions between viruses and the role of stochasticity in transmission, we showed that for the same dataset our model predicts a scenario of coexistence between strains and reveals a higher transmitted viral load", concludes the researcher.

The advantage of this framework lies in its simplicity and generality: the model can be applied to other ecological scenarios of microbial competition, while allowing exploration of more outcomes from the competitive dynamics between two strains.

This study was developed at Instituto Gulbenkian de Ciência and in collaboration with the Master program in Biostatistics at the Faculty of Sciences, University of Lisbon.

Credit: 
Instituto Gulbenkian de Ciencia

An enhanced ruthenium-based catalyst for primary amine synthesis

image: Direct amination of alcohols over Ru-MgO/TiO2 activated by electron donation from MgO.

Image: 
Yusuke Kita

Researchers at Tokyo Institute of Technology (Tokyo Tech) have developed a high-performance reusable ruthenium-based catalyst for the production of primary amines. Their method represents a major advance for the development of efficient catalysts that enable selective conversion of alcohols into primary amines under mild reaction conditions.

Primary amines are extremely versatile building blocks that are used in the preparation of many kinds of dyes, detergents, pharmaceuticals and agricultural chemicals. So far, several methods have been developed to produce primary amines using catalysts containing ruthenium, cobalt and platinum, all of which require the addition of molecular hydrogen. Synthesis of primary amines by direct substitution of alcohols with ammonia has been a longstanding challenge.

Now, researchers at Tokyo Tech report a heterogeneous[1] ruthenium-based catalyst (Ru-MgO/TiO2) capable of driving direct amination[2] of alcohols to produce primary amines without having to introduce hydrogen gas. They showed that the catalyst works at low temperatures, of around 100°C. The ready availability of alcohols and low cost of ammonia make the system both cost-effective and environmentally friendly.

Compared with previous ruthenium-based systems, Ru-MgO/TiO2 achieved higher yields (up to 94%) of the desired primary amines. Reuse experiments showed that after base treatment, the catalyst could be reused three times without significant loss of activity.

Their study, published in Chemical Science, suggests that the MgO component of the catalyst plays an important role in enhancing reactivity through electron donation from MgO to Ru.

The researchers point out that the new catalytic system could be applied to a variety of alcohols, and could serve as a design guide for other new heterogeneous catalysts.

In addition, Ru-MgO/TiO2 could provide an efficient synthetic route for the production of 2,5-bis(aminomethyl)furan (BAMF), an attractive compound used as a hardener for epoxy resins, which are used in many types of coatings and adhesives. Using biomass-derived 2,5-bis(hydroxymethyl)furan (BHMF) as a substrate, the study showed the desired BAMF was obtained at 86% yield, outperforming previous systems.

Credit: 
Tokyo Institute of Technology

Primate brain size does not predict their intelligence

video: For the first time a research team from the German Primate Centre (DPZ) - Leibniz Institute for Primate Research in Göttingen has systematically investigated the cognitive abilities of three lemur species, which have relatively small brains compared to other primates.

Image: 
Katja Rudolph

Chimpanzees, gorillas and orangutans are our closest relatives, and like us they have relatively large brains and they are very intelligent. But do animals with larger brains really perform better in cognitive tests? A research team from the German Primate Center (DPZ) - Leibniz Institute for Primate Research in Göttingen has for the first time systematically investigated the cognitive abilities of lemurs, which have relatively small brains compared to other primates. Conducting systematic tests with identical methods revealed that cognitive abilities of lemurs hardly differ from those of monkeys and great apes. Instead, this study revealed that the relationship between brain size and cognitive abilities cannot be generalized and it provides new insights into the evolution of cognitive abilities in primates.

Humans and non-human primates are among the most intelligent living beings. Their brain size may underly their intelligence as primates have relatively large brains in relation to their body size. For example, it is assumed that larger brains enable faster learning and better memory capacities. Within primates, however, species can differ up to 200-fold in brain size. A team of researchers from the German Primate Center (DPZ) has now investigated whether the cognitive performances of lemurs with their relatively small brains differ from those of other primates.

Using a comprehensive standardized test series of cognitive experiments, the so-called "Primate Cognition Test Battery" (PCTB), small children, great apes as well as baboons and macaques have already been tested for their cognitive abilities in the physical and social domain. Cognitive skills in the physical domain include the understanding of spatial, numerical and causal relationships between inanimate objects, while cognitive skills in the social domain deal with intentional actions, perceptions and the understanding of the knowledge of other living beings. Initial studies have shown that children possess a better social intelligence than non-human primates. In the physical domain, however, the species hardly differed even though they show great variation in their relative brain sizes.

For the first time, researchers of the "Behavioral Ecology and Sociobiology Unit" of the DPZ have now tested three lemur species with the PCTB. Lemurs are the most basal living primates and represent the evolutionary link between primates and other mammals, which is why they serve as a living model of primates' origin of cognitive abilities. The study examined ring-tailed lemurs, black-and-white ruffed lemurs and grey mouse lemurs, which differ in their social system, diet and brain size, not only among each other, but also compared to the previously tested Old World monkeys and great apes.

The results of the new study show that despite their smaller brains lemurs' average cognitive performance in the tests of the PCTB was not fundamentally different from the performances of the other primate species. This is even true for mouse lemurs, which have brains about 200 times smaller than those of chimpanzees and orangutans. Only in tests examining spatial reasoning primate species with larger brains performed better. However, no systematic differences in species performances were neither found for the understanding of causal and numerical relationships nor in tests of the social domain. Neither diet, nor social system or brain size could explain the results from the PCTB experiments. "With our study we show that cognitive abilities cannot be generalized, but that species instead differ in domain-specific cognitive skills," says Claudia Fichtel, one of the two first authors of the study funded by the German Research Foundation. "Accordingly, the relationship between brain size and cognitive abilities cannot be generalized".

The study represents the first systematic and comparative investigation of cognitive abilities in lemurs and provides important insights into the evolution of cognitive abilities in primates. However, the research team also emphasizes that further comparative studies in a variety of other species are essential to answer the many questions about the relationship between brain size, diet, social life and cognition.

Credit: 
Deutsches Primatenzentrum (DPZ)/German Primate Center

"Stretching rack" for cells

image: Electron micrograph of the "empty" scaffold (without hydrogel) that an international research team used to deform individual cells.

Image: 
Marc Hippler, KIT

The behavior of cells is controlled by their environment. Besides biological factors or chemical substances, physical forces such as pressure or tension are also involved. Researchers from Karlsruhe Institute of Technology (KIT) and Heidelberg University developed a method that enables them to analyze the influence of external forces on individual cells. Using a 3D printing process, they produced micro-scaffolds, each of which has four pillars on which a cell is located. Triggered by an external signal, a hydrogel inside the scaffold swells and pushes the pillars apart, so that the cell must "stretch." The work is part of the "3D Matter Made to Order" (3DMM2O) Cluster of Excellence. The researchers report on their results in Science Advances (DOI: 10.1126/sciadv.abc2648).

Many cellular biological processes, such as wound healing or the development of tissue, are strongly influenced by the properties of their environment. Cells react, for example, to biological factors or chemical substances. However, research is increasingly focusing on physical forces acting on the cells: How exactly do the cells adapt to these forces?

Within the framework of the German-Japanese University Consortium HeKKSaGOn and in cooperation with Australian scientists, the 3DMM2O team has taken a particularly ingenious approach to this question. For the production of their cell "stretching racks" they used "direct laser writing", a special 3D printing process in which a computer-controlled laser beam is focused into a special printer ink liquid. Its molecules react only at the exposed areas and form a solid material there. All other areas remain liquid and can be washed away. "This is an established method in our Cluster of Excellence for building three-dimensional structures - on the micrometer scale and below," explains Marc Hippler from the KIT Institute of Applied Physics, lead author of the publication.

In the current case, the researchers used three different printer inks: The first ink, made of protein-repellent material, was used to form the actual micro-scaffold. Using a second ink of protein-attracting material, they then produced four horizontal bars that are connected to one of the scaffold pillars each. The cell is anchored to these four bars. The real showstopper, however, is the third ink: The scientists used it to "print" a mass inside the scaffold. If they then add a special liquid, the hydrogel swells. It thus develops a force sufficient to move the pillars - and the bars with them. This, in turn, has the effect of stretching the cell that is fixed to the bars.

Cells counteract deformation

The scientists of the Cluster of Excellence placed two completely different cell types on their micro stretching rack: human bone tu-mor cells and embryonic mouse cells. They found that the cells counteract the external forces with motor proteins and thus greatly increase their tensile forces. When the external stretching force is removed, the cells relax and return to their original state. "This be-havior is an impressive demonstration of the ability to adapt to a dynamic environment. If the cells were unable to recover, they would no longer fulfill their original function - for example wound closure," says Professor Martin Bastmeyer from the Zoological Institute of KIT.

As the team further discovered, a protein called NM2A (non-muscle myosin 2A) plays a decisive role in the cells' response to mechani-cal stimulation: Genetically modified bone tumor cells that cannot produce NM2A were barely able to counteract the external defor-mation.

Work in the cluster of excellence was carried out by Heidelberg scientists from the field of biophysical chemistry as well as physics and cell- and neurobiology from KIT. Members of the German-Japanese University Consortium HeKKSaGOn include, among oth-ers, Heidelberg University, Karlsruhe Institute of Technology and Osaka University.

Cluster of Excellence 3D Matter Made to Order

In the 3D Matter Made to Order (3DMM2O) Cluster of Excellence, scientists of Karlsruhe Institute of Technology and Heidelberg Uni-versity conduct interdisciplinary research into innovative technolo-gies and materials for digital scalable additive manufacture to en-hance the precision, speed, and performance of 3D printing. Work is aimed at completely digitizing 3D manufacture and materials pro-cessing from the molecule to the microstructure. In addition to fund-ing as a cluster of excellence under the Excellence Strategy compe-tition launched by the federation and the federal states, 3DMM3O is financed by Carl Zeiss Foundation.

Credit: 
Karlsruher Institut für Technologie (KIT)