Tuesday, December 05, 2023

HIVES

Unravelling the mechanism of urticaria from eruption shapes

Innovation for developing new treatments based on eruption morphology in mathematical dermatology

INSTITUTE FOR THE ADVANCED STUDY OF HUMAN BIOLOGY (ASHBI)

Unravelling the mechanism of urticaria from eruption shapes — IMAGE:
A RESEARCH GROUP LED BY PROFESSOR SUNGRIM SEIRIN-LEE AT KYOTO UNIVERSITY INSTITUTE FOR THE ADVANCED STUDY OF HUMAN BIOLOGY (WPI-ASHBI) LEVERAGED HIERARCHICAL MATHEMATICAL MODELING TO ANALYZE THE SHAPES OF SKIN ERUPTIONS AND LINK THESE MORPHOLOGICAL FEATURES TO THE IN VIVO PATHOLOGICAL DYNAMICS OF CHRONIC SPONTANEOUS URTICARIA CSU.
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CREDIT: KANON TANAKA (HTTPS://WWW.KANONTANAKA-ILLUSTRATION-WEBDESIGN-SCIENCE.COM/INDEX.HTML)

The skin is the largest organ in the human body and plays an important role in maintaining homeostasis as well as protecting the body from the outside environment. Skin diseases can be life-threatening or heavily impair patients’ quality of life. Urticaria (also called “hives”) is common, affecting at least one in five people in their lifetime, and can persist for years or even decades. Many skin diseases are unique to humans, and their pathogenesis often remains unclear due to the lack of an appropriate experimental animal model and limited clinical data. One such human-specific disease is chronic spontaneous urticaria (CSU), which is characterized by the appearance of skin eruptions called wheals, which have a range of sizes and shapes and are accompanied by itching.

Despite CSU having a clear and visible appearance on the skin surface, the mechanism underlying the various shapes of wheals in vivo remains largely obscured. Recently, a number of pathophysiological characteristics of urticaria have been investigated, including autoimmune responses, cellular infiltrates, and activation of the coagulation pathway by the complement system. It is therefore of great importance to integrate these elements into their dynamics in vivo in order to develop more effective patient-specific treatments.

To address this, a research group led by Professor Sungrim Seirin-Lee at Kyoto University Institute for the Advanced Study of Human Biology (WPI-ASHBi) leveraged hierarchical mathematical modeling to analyze the shapes of skin eruptions and link these morphological features to the in vivo pathological dynamics of CSU. By incorporating both the intravascular and extravascular dynamics using in vitro experimental data, they classified the skin eruption patterns into five potential types. Using these patterns, the researchers developed the Criteria for Classification of Eruption Geometry (EGe criteria) according to their relations with tissue factor and histamine dynamics of mast cells, which act on blood vessels and induce wheal formation. The researchers then demonstrated the validity of their mathematical model to classify CSU according to these criteria in 105 patients, and found the reliability to be as high as 87.6% when analyzed by dermatologists.

“This study was the first to use mathematical models to clarify the pathophysiology of skin eruptions according to their morphology, and can help to pave the way for alternative treatment methods. For example, patients might take photos of their skin eruptions to provide data for a definitive diagnosis of underlying causes, or the effectiveness of treatment can be monitored over time. In addition, this study shows the promise of mathematical models in the understanding the mechanisms of human-specific diseases, where animal models are not available,” Seirin-Lee said.

Through these efforts, the authors hope to pioneer mathematical dermatology as a new multidisciplinary research field for practical use, integrating mathematical science and clinical dermatology for elucidating the pathophysiology of skin diseases and developing new strategies for managing intractable skin diseases.

Paper Information

Sungrim Seirin-Lee, Daiki Matsubara, Yuhki Yanase, Takuma Kunieda, Shunsuke Takahagi, and Michihiro Hide (2023) Mathematical-structure based Morphological Classification of Skin Eruptions and Linking to the Pathophysiological State of Chronic Spontaneous Urticaria, Communications Medicine

JOURNAL

Communications Medicine

DOI

10.1038/s43856-023-00404-8

METHOD OF RESEARCH

Computational simulation/modeling

ARTICLE PUBLICATION DATE

4-Dec-2023

Small publishers increasingly important for translated literature

Reports and Proceedings

UPPSALA UNIVERSITY

Over the period 1970–2016, small publishing houses became increasingly important for the publication of literature in translation in Sweden. More than ever, Nobel laureates are being published by relatively small independent publishers. A specialisation in translations often stems from a publisher’s personal interest in a language or geographical area. These conclusions are drawn in a doctoral thesis submitted at Uppsala University.

“It’s remarkable how quickly the small publishers became major actors for translated literature in the Swedish book market. Between 1978 and 1997, ten future recipients of the Nobel Prize in Literature were introduced in Swedish translation by a small publishing house founded after 1975. This is an important factor to consider, since publishing these authors before they are awarded the Nobel Prize entails a greater financial risk for a publisher than after the prize, when publication can be associated with prestige and guaranteed attention,” says Jana Rüegg, Doctor in literature, Uppsala University.

Many new publishing houses were founded after the introduction of state subsidies for literature in 1975 and several of them rapidly became important specifically for translations. Another wave of newly established small publishers has entered the market since the beginning of the 21st century. They have taken on a vital role in the publication of translations in Sweden, particularly from major languages such as French, German and Spanish.

In the years around 2010, several large publishers experienced financial crises, which led them to let go of translated authors whom other publishers were then able to take over, as the thesis shows. The small publishers have also influenced the selection of authors translated into Swedish.

“Over the period 1970–2000, numerous editions of works primarily by male writers were published, translated from the major languages French, German and Spanish. This was partly because of the very extensive publication of classics, which are a type of literature associated in this context with male authors such as Jules Verne, Franz Kafka or Marcel Proust,” says Rüegg.

Her research shows that small publishers founded in the 21st century have played an enormously important role in the publication of translations of works by female writers from French, German and Spanish. After 2005, the gap has narrowed and around 40 per cent of published translations from those three languages have female authors.

The thesis consists of two parts.

The first part, Nobelbanor (Nobel Trajectories), studies translated Nobel laureates in literature between 1970 and 2016 on the Swedish book market and whether they were published before or after the Nobel Prize. The study is based on a dataset of all editions of these authors in Swedish translation up to 2017.

To a large extent, the 45 Nobel Prize laureates were available in Swedish translation before the prize. The fact that 49 per cent of them were published in paperback editions before being awarded the prize shows that the publishers saw a potential demand for large editions of these authors. On average, 20 years passes between the first Swedish translation and the Nobel Prize, which means that in many cases, the Nobel Prize reawakens an interest in an author who has been forgotten by the Swedish book market since their first introduction.

Over time there is a clear migration from larger to smaller publishers in the publication of translated Nobel laureates.

The second part of the thesis, Förmedla och förlägga (Transmit and Publish), focuses on translations from French, German and Spanish published by Swedish publishers between 1970 and 2016. The study is based on a dataset of all fiction editions for adults translated from the three languages in Sweden from 1970 to 2016.

Over time, the number of translations from French and German has decreased and towards the end of the period studied, these translations were increasingly published by small niche publishers rather than large publishing houses. Translations from Spanish follow a different pattern, because it was not until the 1980s that Swedish publishers seriously began publishing translations from that language, including big names such as Gabriel García Márquez and Isabel Allende.

Large publishers continue to publish translations from Spanish to a greater extent, even towards the end of the period studied. According to Rüegg, the historical status of the languages on the Swedish book market clearly plays a role in determining what is translated and published.

“In French and German, there is a long tradition of publication in Sweden and here we find translations from a wide range of genres, from classics and Nobel laureates to popular fiction. Translations from Spanish do not have such a long tradition of publication in the Swedish book market, which has led to very few Spanish-language classics being translated and published and also to relatively limited publication of popular Spanish-language literature in translation during this period,” Rüegg concludes.

METHOD OF RESEARCH

Commentary/editorial

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Publishing Translations: Flows, Patterns, and Power-Dynamics in the Swedish Book Market after 1970

ARTICLE PUBLICATION DATE

4-Dec-2023

Tiny electromagnets made of ultra-thin carbon

When terahertz pulses strike graphene discs

Peer-Reviewed Publication

HELMHOLTZ-ZENTRUM DRESDEN-ROSSENDORF

HZDR's FELBE free-electron lasers — IMAGE:
DR. STEPHAN WINNERL (RIGHT) TALKS TO FELBE PHYSICIST DR. JOHN MICHAEL KLOPF ABOUT EXPERIMENTS AT THE HZDR'S FELBE FREE-ELECTRON LASERS.
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CREDIT: HZDR/OLIVER KILLIG

Graphene, that is extremely thin carbon, is considered a true miracle material. An international research team has now added another facet to its diverse properties with experiments at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR): The experts, led by the University of Duisburg-Essen (UDE), fired short terahertz pulses at micrometer-sized discs of graphene, which briefly turned these minuscule objects into surprisingly strong magnets. This discovery may prove useful for developing future magnetic switches and storage devices. The working group presents its study in the scientific online journal Nature Communications (DOI: 10.1038/s41467-023-43412-x).

Graphene consists of an ultra-thin sheet of just one layer of carbon atoms. But the material, which was only discovered as recently as 2004, displays remarkable properties. Among them is its ability to conduct electricity extremely well, and that is precisely what international researchers from Germany, Poland, India, and the USA took advantage of.

They applied thousands of tiny, micrometer-sized graphene discs onto a small chip using established semiconductor techniques. This chip was then exposed to a particular type of radiation situated between the microwave and infrared range: short terahertz pulses.

To achieve the best possible conditions, the working group, led by the UDE, used a particular light source for the experiment: The FELBE free-electron laser at the HZDR can generate extremely intense terahertz pulses. The astonishing result: "The tiny graphene disks briefly turned into electromagnets," reports HZDR physicist Dr. Stephan Winnerl.

"We were able to generate magnetic fields in the range of 0.5 Tesla, which is roughly ten thousand times the Earth's magnetic field." These were short magnetic pulses, only about ten picoseconds or one-hundredth of a billionth of a second long.

Radiation pulses stir electrons

The prerequisite for success: The researchers had to polarize the terahertz flashes in a specific way. Specialized optics changed the direction of oscillation of the radiation so that it moved, figuratively speaking, helically through space.

When these circularly polarized flashes hit the micrometer-sized graphene discs, the decisive effect occurred: Stimulated by the radiation, the free electrons in the discs began to circle – just like water in a bucket stirred with a wooden spoon. And because, according to the basic laws of physics, a circulating current always generates a magnetic field, the graphene disks mutated into tiny electromagnets.

"The idea is actually quite simple," says Martin Mittendorff, professor at the University of Duisburg-Essen. "In hindsight, we are surprised nobody had done it before." Equally astonishing is the efficiency of the process: Compared to experiments irradiating nanoparticles of gold with light, the experiment at the HZDR was a million times more efficient – an impressive increase. The new phenomenon could initially be used for scientific experiments in which material samples are exposed to short but strong magnetic pulses to investigate certain material properties in more detail.

The advantage: "With our method, the magnetic field does not reverse polarity, as is the case with many other methods," explains Winnerl. "It, therefore, remains unipolar." In other words, during the ten picoseconds that the magnetic pulse from the graphene disks lasts, the north pole remains a north pole and the south pole a south pole – a potential advantage for certain series of experiments.

The dream of magnetic electronics

In the long run, those minuscule magnets might even be useful for certain future technologies: As ultra-short radiation flashes generate them, the graphene discs could carry out extremely fast and precise magnetic switching operations. This would be interesting for magnetic storage technology, for example, but also for so-called spintronics – a form of magnetic electronics.

Here, instead of electrical charges flowing in a processor, weak magnetic fields in the form of electron spins are passed on like tiny batons. This may, so it is hoped, significantly speed up the switching processes once again. Graphene disks could conceivably be used as switchable electromagnets to control future spintronic chips.

However, experts would have to invent very small, highly miniaturized terahertz sources for this purpose – certainly still a long way to go. "You cannot use a full-blown free-electron laser for this, like the one we used in our experiment," comments Stephan Winnerl. "Nevertheless, radiation sources fitting on a laboratory table should be sufficient for future scientific experiments." Such significantly more compact terahertz sources can already be found in some research facilities.

Publication:

J.W. Han, P. Sai, D-B. But, E. Uykur, S. Winnerl, G. Kumar, M.L. Chin, R.L. Myers-Ward, M.T. Dejarld, K.M. Daniels, T.E. Murphy, W. Knap, M. Mittendorff: Strong transient magnetic fields induced by THz-driven plasmons in graphene disks, Nature Communications, 2023, (DOI: 10.1038/s41467-023-43412-x)

The Helmholtz-Zentrum Dresden-Rossendorf (HZDR) performs – as an independent German research center – research in the fields of energy, health, and matter. We focus on answering the following questions:

• How can energy and resources be utilized in an efficient, safe, and sustainable way?

• How can malignant tumors be more precisely visualized, characterized, and more effectively treated?

• How do matter and materials behave under the influence of strong fields and in smallest dimensions?

To help answer these research questions, HZDR operates large-scale facilities, which are also used by visiting researchers: the Ion Beam Center, the Dresden High Magnetic Field Laboratory and the ELBE Center for High-Power Radiation Sources.

HZDR is a member of the Helmholtz Association and has six sites (Dresden, Freiberg, Görlitz, Grenoble, Leipzig, Schenefeld near Hamburg) with almost 1,500 members of staff, of whom about 670 are scientists, including 220 Ph.D. candidates.

The electrons from the ELBE accelerator generate laser light in one of the two blue-metallic magnetic structures, the so-called undulators.

CREDIT

HZDR/Christoph Reichelt

When a circularly polarized light pulse (red) hits a micrometre-sized graphene disc (grey), a magnetic field is created for a fraction of an instant (black lines).

CREDIT

Lucchesi, Uta (HZDR)