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Precision medicine for chronic inflammatory diseases

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News, Pharmaceuticals

Paratyphoid fever is an infectious disease with high fever, abdominal pain and nausea, sometimes also diarrhea, which can be fatal if left untreated. It is similar to the better known typhoid fever, but is caused by a different bacterial pathogen. While paratyphoid fever has become very rare in Germany and Europe today, paratyphoid epidemics continue to occur occasionally in Asia, especially after natural disasters such as floods. In the Middle Ages, however, paratyphoid caused epidemics in Europe with high numbers of victims.

Researchers of the Cluster of Excellence “Precision Medicine in Chronic Inflammation” (PMI) have now for the first time studied human immunogenetics to typhoid fever in Europe in more detail and identified a risk gene that makes people more susceptible to paratyphoid fever. This risk gene is still present in the European population today and at the same time increases the risk for modern inflammatory diseases such as multiple sclerosis or type I diabetes. The team led by Professor Ben Krause-Kyora, an archaeologist and biochemist at the Institute of Clinical Molecular Biology (IKMB) at Kiel Christian Albrechts University (CAU) and Schleswig-Holstein University Hospital (UKSH), Kiel Campus, recently published its findings in the journal Frontiers in Immunology.

In the early 1990s, the remains of numerous people who were buried there in the course of several mass burials in the Middle Ages were found during reconstruction work at the Holy Spirit Hospital in Lübeck. Distributed among various pits of different sizes, a total of more than 800 skeletons of all genders and ages were recovered, which could be dated to the second half of the 14th century. In a previous work, Krause-Kyora’s team isolated and analyzed so-called aDNA, or ancient DNA, from 92 skeletons. This allowed them to identify the causative agent of paratyphoid fever, Salmonella enterica subsp. enterica Paratyphi C, in the remains, showing that the people in the mass grave had died in the wake of a paratyphoid epidemic.

“Now we have also analyzed the genes of these deceased people, which are important for the immune system and thus for fighting such pathogens, using the DNA that is still present.”

– Krause-Kyora, a member of the PMI Cluster of Excellence

In this way, the researchers were able to identify a risk gene that was particularly prevalent in the deceased from the mass grave compared to the overall population at the time. “This gene variant apparently meant that the immune systems of people who had these variants were not as good at fighting off the paratyphoid pathogen and were therefore more likely to contract it,” explains Magdalena Haller, first author of the paper and a doctoral student in the “aDNA Analysis” working group at the IKMB. The gene variant has already been described for people in Asia in connection with paratyphoid fever, but there have been no studies for Europe so far.

The gene variant HLA-DRB1*03:01 is located in the gene region that is important for a specific immune response against bacteria and viruses. With the help of computer modeling, the team was able to find further evidence that people with this variant are less effective at warding off the paratyphoid pathogen.

“We calculated how well the structures encoded by the gene bind to the paratyphoid pathogen,” explains co-author Professor Tobias Lenz from the University of Hamburg and the Max Planck Institute for Evolutionary Biology in Plön, also a member of the PMI Cluster of Excellence. “Thus, we were able to show that the structures encoded by this gene variant presumably bind worse to the pathogen of paratyphoid fever and can therefore fight it more poorly than with other variants of this gene. This would explain why a particularly large number of people with this variant have died from paratyphoid,” Lenz added.

The gene variant that makes people more susceptible to paratyphoid fever is still found in people in Europe today. Studies have shown that it may also play a role in modern inflammatory diseases. For example, it favors unwanted immune reactions to components from food, i.e. food allergies, but also inflammatory diseases such as multiple sclerosis (MS) and type I diabetes. At the same time, however, this variant is also associated with a certain protection against lung diseases such as tuberculosis.

It is precisely because of such connections that Krause-Kyora and his team are studying ancient pathogens and ancient human DNA. “Insights into the evolution of such diseases and the human immune system can contribute to a better understanding of how modern diseases of the immune system, such as chronic inflammatory diseases, develop,” Krause-Kyora explains.

 

News Processing Technologies

Rapid further development of connectors

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The Connector Congress in Würzburg has come to an end with the participation of rolled products manufacturer Kemper.

“After more than a year of abstinence, finally the first presence event in the industry. A piece of normality that many have longed for all this time. We are all the more pleased to have had many interesting discussions and made new contacts.”

– Dr. Stephan Hansmann, Head of Technical Marketing

Miniaturization is one of the much-discussed megatrends, as a result of which more and more plug contacts are being realized in the smallest possible installation space. Accordingly, there was great interest at the Kemper booth in HP bronzes, which have improved formability compared to standard alloys without sacrificing strength. With this property, Kemper HP bronzes offer themselves as an optimal material for increasingly smaller connector systems. “Connectors in particular are developing rapidly and will actively accompany the energy transition,” Hansmann is certain. “This includes, for example, smart connectors with additional functions, where, for example, connectors communicate with each other even before the plugging process has taken place.”

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Great catch-up potential for eMobility in public transport

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Around a hundred thousand diesel buses are still on Europe’s roads with outdated technology. At the same time, the number of e-buses is rising significantly. It is hardly surprising that electromobility is on the rise. After all, the call for sustainable mobility is getting louder and louder. With the MAN Lion’s City 12 E and the all-electric 18 E articulated bus, MAN Truck & Bus offers the right solution for the urban transport of the future.

Electromobility is electrifying more and more people. This is clearly demonstrated by the rising registration figures for e-cars. But e-mobility is not only gaining momentum in private transport. In public transport, too, more and more operators are turning to e-vehicles, as recent figures from the umbrella organization of European vehicle manufacturers (ACEA) show. Based on bus registration figures, the association reported that sales of electric buses in the European Union increased by 18.4 percent in 2020 compared to 2019. The share of diesel engines, on the other hand, decreased by almost ten percent (source: “ACEA buses by fuel type full-year 2020,” 30 March 2021).

“Overall, the total European market for electric buses was more than 2,000 vehicles last year. And the trend is clearly upward. We expect half of all new city buses to be alternatively powered by 2025.”

– Rudi Kuchta, Head Business Unit Bus

Despite the rising eBus numbers, diesel buses are still by far the most common on EU roads. According to ACEA, there were a total of more than 690,000 buses in 2019, with an average age of 11.7 years – 94.5 percent of which were powered by diesel, and 0.6 percent purely electric (source: ACEA Report “Vehicles in use Europe,” January 2021). “The figures and our experience show that electromobility is on the rise. At the same time, they also make clear what great potential it still holds. Replacing diesel buses with outdated technology with modern electric buses will help enormously to reduce CO2 emissions,” says Kuchta, adding, “This is a key building block in tackling climate change.” After all, with an annual mileage of 50,000 to 60,000 kilometers and a consumption of 36 to 49 liters per 100 kilometers, which varies depending on use, topography and vehicle variant, an eBus traveling with zero local emissions can save around 60 to 80 tons of CO2 per year – compared to a diesel bus and assuming the current electricity mix.

The bus is already considered the most environmentally friendly and economical means of transport. However, local public transport operators and municipalities have it in their own hands to cut CO2 emissions even more and thus contribute to climate protection. The European Union has also recognized this and passed the Clean Vehicle Directive. This provides for binding emission standards in municipal fleets – the legislation has been in force since August 2021. Cities must thus set their course for emission-free mobility. The goal: to move from “low emission” to “no emission.”

“More and more public transport companies have understood this and are relying only on battery-powered city buses for new purchases. Or they are setting clear time targets for converting the entire fleet to zero-emission drives,” says Kuchta. One example is Verkehrsbetriebe Hamburg-Holstein (VHH), which has been procuring only locally emission-free, battery-powered buses since 2020. The goal is to convert the entire bus fleet to zero-emission drives as far as possible by 2030.

In order to provide transport companies with the best possible support on their way to zero-emission mobility, the company offers an overall concept that brings together holistic eMobility consulting and tailored, forward-looking solutions. Because for MAN, too, the future of urban mobility is electric. “We are convinced that electromobility is the key technology for commercial vehicle transport of the future. For this reason, we are constantly driving technologies and progress forward together with our customers,” says Rudi Kuchta. The focus here is on the MAN Lion’s City E – and thus the all-electric solution for public transport.

For months now, the MAN Lion’s City E has been demonstrating in more and more cities throughout Europe how excellently it masters urban traffic and how easily it can be integrated into existing processes. During an MAN eBus test drive that took place in Munich in May of this year, it also cracked the 550-kilometer mark under realistic everyday conditions with just one battery charge. “The issue of range plays an essential role for our customers.

After all, on lines that were previously served by a single vehicle with an internal combustion engine, only one electric vehicle will be on the road in the future. During the MAN Efficiency Run, our eBus impressively demonstrated how suitable electric mobility already is for everyday use,” says Kuchta. Even with a realistic range of “only” 400 kilometers in regular operation, the bus could cover 98 percent of the routes served by MAN customers without intermediate charging. And it would then be charged in the depot – with the advantage that operators would not have to invest in additional charging infrastructure in the city area.

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News Processing Technologies Water & Waste Water

WPL wastewater technology is selected by major logistics hub

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Technology from water recycling specialist WPL, a WCS Group company, was selected by DP World London Gateway to provide enhanced ammonia removal to protect sensitive waters in the Thames Estuary. 

DP World London Gateway is a smart logistics center on the north bank of the Thames in Thurrock, Essex, 25 miles from central London. The water recycling specialist will supply a bespoke treatment plant for a new freestanding warehouse for 150 office workers, currently under construction at the logistics center. The plant will be able to handle a flow of 7.5 m3/d for 100 population equivalents.

The treatment plant will discharge into an environmentally sensitive swale that empties into the Thames Estuary and must meet the Environment Agency’s stringent standards of 15:15:03 mg/l for ammonia and suspended solids.  The water specialist will provide an underground HiPAF (High Performance Aerated Filter) system for ammonia removal, as well as a metering unit and sand filter to further improve the final effluent in accordance with site-specific permit requirements. The design also includes a small pumping system due to the depth of the incoming effluent and a pumped backflow chamber.

Dominic Hamblin, WPL’s technical director, said, “DP London Gateway is a key logistics hub and we are pleased to be able to deliver this environmental solution on site on its behalf.

“WPL’s modular HiPAF product range meets the stringent European standards for permitting wastewater without the use of chemicals. The technology is regularly used by UK water utilities and is a good choice for sensitive sites such as marshes, which are shallow and not heavily diluted.

“The HiPAF’s compact design allows it to be installed in locations where space is at a premium, such as a busy commercial area. In addition, our sand filters are designed to remove excess suspended solids and biological oxygen demand when permit standards are above what would normally be expected from a biological process. 

“Once operational, the plant will provide robust wastewater treatment while being quiet, visually unobtrusive and easy to maintain. WPL’s wastewater treatment plant is being built by Readie Construction. Construction is scheduled to begin before the end of 2021 and is expected to take 12 weeks.

“DP World London Gateway is a high-profile site surrounded by sensitive water bodies. We are therefore pleased to be working with WPL to install on-site wastewater treatment for the new warehouse building.”  

– Giuseppe Orlando, Project Manager 

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