Patients who arrive at the hospital with heart-attack-like symptoms have had little recourse for their chest pain if scans came back clear, with no signs of blocked coronary arteries. Some of these cases are caused by a little-known phenomenon called coronary slow flow. Now, researchers at Jefferson (Philadelphia University + Thomas Jefferson University), have demonstrated for the first time a simple technique to effectively treat this under-recognized condition. They published their findings in the Journal of Invasive Cardiology on December 15. "One of the biggest issues with coronary slow flow is that many cardiologists aren't familiar with it and don't know what to look for to diagnose it," said senior author Michael Savage, MD, Director of the Cardiac Catheterization Lab at the Sidney Kimmel Medical College at Thomas Jefferson University. "Here we've shown that once you do recognize it, the condition can be treated with an existing and safe medical intervention that reverses the problem." Not a lot is known about the coronary slow flow. It is identified by angiogram of the heart, revealing arteries that fill with blood more slowly than normal, even in the absence of fatty plaque deposits. But what causes the condition, and why in 80 percent of cases patients experience additional episodes of chest pain, is still unknown. One association that can be drawn, says first author Hetal H. Mehta, MD, a cardiology fellow at Jefferson, is that smokers are two-to-three times more likely to experience the phenomenon. When Dr. Savage and others first saw the condition on angiograms of their patients, it appeared similar to the no-reflow phenomenon caused by microvascular spasm during coronary angioplasty procedures. Since that condition could be treated with a drug called nicardipine, Dr. Savage and colleagues decided to test it with their coronary slow flow patients. "It worked incredibly well," he said. In this study, the researchers analyzed the data and outcomes of 30 patients with coronary slow flow who were treated during cardiac catheterization with an intracoronary injection of nicardipine . They found a total of 49 blood vessels with slow blood flow. After treatment with nicardipine, all of the vessels showed normalized blood flow. "These results suggest that microvascular spasm may be responsible for this condition, which can be effectively reversed with a calcium channel blocker like nicardipine," said Dr. Savage. "It's a simple intervention that takes only a few seconds to administer, and helps diagnose the condition and treat it at the same time." Nicardipine appears to reverse the condition in the short term, but future studies are needed to explore whether the one-time treatment reverses the condition permanently, or whether patients would benefit from long-term use of an oral calcium channel blocker.
Researchers from the University of Chicago have developed a high-throughput RNA sequencing strategy to study the activity of the gut microbiome. The new tools analyze transfer RNA (tRNA), a molecular Rosetta Stone that translates the genetic information encoded in DNA into proteins that perform basic biological functions. Developing a clear picture of tRNA dynamics will allow scientists to understand the activity of naturally occurring microbiomes, and study their responses to environmental changes, such as varying temperatures or changing availability of nutrients. In a new study published in Nature Communications, a team of scientists led by Tao Pan, PhD, professor of biochemistry and molecular biology, and A. Murat Eren, PhD, assistant professor of medicine at UChicago, demonstrated the application of tRNA sequencing to gut microbiome samples from mice that were fed either a low-fat or high-fat diet. The new software and computational strategy described in the study created a catalog of tRNA molecules recovered from the gut samples, traced them back to the bacteria responsible for their expression, and measured chemical modifications in tRNA that take place after transcription. Each tRNA in bacteria has an average of eight chemical modifications that can tune its function. The new high-throughput sequencing and analysis strategy detects two of them, but it can also measure the amount of modification on a scale from 0 to 100 percent at each site. The level of one of the modifications, called m1A, was higher in the gut microbiome of mice that were fed a high-fat diet. This is the first time scientists have been able to see any modification level change in tRNA in any microbiome. "We were working backwards," Pan said. "We had no preconceived notion of why the m1A tRNA modifications were actually there or what they were doing, but to see any modification change at all in the microbiome is unprecedented." The m1A modification helps synthesize certain types of proteins that may be more abundant in a high-fat diet. The researchers don't know yet if these modification differences occur in response to that diet, or if they are already present and become active to enhance the synthesis of those proteins. The study is the first of a series of microbiome projects from UChicago funded by a grant from the Keck Foundation. Pan has pioneered the use of tRNA sequencing tools, and the grant will fund continuing work to make them widely accessible through new computational strategies that Eren develops. Large sets of data generated by tRNA sequencing can provide critical insights into microbiomes associated with humans or the environment at a low cost. "The molecular and computational advances that have emerged during the last two decades have only helped us scratch the surface of microbial life and their influence on their surroundings," Eren said. "By providing quick and affordable insights into the core of the translational machinery, tRNA sequencing may become not only a way to gain insights into microbial responses to subtle environmental changes that can't be easily measured by other means, but also bring more RNA biology and RNA epigenetics into the rapidly developing field of the microbiome." Pan and Eren agree that there is much room to improve this novel strategy, and they hope that it will happen quickly. "There are a number of ways to examine microbiome activities, but nothing is faster and gets you more volume of data than sequencing," Pan said. "Here we have developed a new method that reports activity of the microbiome through tRNA and does so at high throughput. That's really the value." The study, "Microbiome characterization by high-throughput transfer RNA sequencing and modification analysis," was supported by the National Natural Science Foundation of China, Shandong Provincial Natural Science Foundation, China Scholarship Council, the National Institutes of Health, the University of Chicago and the Keck Foundation.
The most important features of the EtherCAT real-time Ethernet fieldbus system include its diagnostic hardware and software options: the system not only detects faults in the EtherCAT network, but also locates them, including loose plug connections. This makes the approach ideal for building a robust industrial network environment. The fault diagnosis allows potential downtimes in a production plant to be prevented. Third-party vendors who can work with any EtherCAT master implementation without additional hardware customization can now use the software-based, low-memory diagnostic interface. Integrating the interface into the in-house diagnostic tool allows the direct retrieval of information about the network topology, comparison with the expected configuration as well as the detection of transmission disturbances and unexpected status changes of the slave devices used. The EtherCAT communication protocol is used to connect a wide range of peripherals and is supported, for example, by the PCRM robot control module from Pilz .
Immersing deeper and deeper into cells with the microscope. Imaging the nucleus and other structures more and more accurately. Getting the most detailed views of cellular multi-protein complexes. All of these are goals pursued by the microscopy expert Markus Sauer at the Biocenter of Julius-Maximilians-Universität Würzburg (JMU) in Bavaria, Germany. Together with researchers from Geneva and Lausanne in Switzerland, he has now shown that a hitherto doubted method of super-resolution microscopy is reliable. We are talking about ultrastructural expansion microscopy (U-ExM). In a nutshell, it works like this: The cell structures to be imaged, in this case multi-protein complexes, are anchored in a polymer – just like decorating a Christmas tree. Then the interactions between the proteins are destroyed and the polymer is swelled with liquid. "The polymer then expands uniformly in all spatial directions by a factor of four. The antigens are retained and can subsequently be stained with dye-labeled antibodies," says Professor Sauer. So far, many scientists have been of the opinion that the expansion of the polymer does not proceed uniformly and one gets a distorted representation in the end. "With U-ExM, we can really depict ultrastructural details, the method is reliable," says Sauer. "And it delivers a picture that is four times higher resolved than with standard methods of microscopy." The research team is currently proving this in the journal "Nature Methods" using the example of the centrioles. These cylindrical protein structures play an important role in cell division; the Würzburg biologist Theodor Boveri first described it in 1888. The centrioles were chosen for the experiment because their structure is already well known. "This enabled us to see, in comparison to electron micrographs, that U-ExM works reliably and even preserves the chirality of the microtubule triplets that make up the centrioles," explains Sauer. Next, the JMU researchers want to use this method of microscopy to analyze cell structures of which one has not yet had such a precise picture. "These are, for example, substructures of the centrioles, the nuclear pore complexes or synaptonemal complexes. All of them are now accessible for the first time with molecular resolution by light microscopy, "said Sauer.
These days, pretty much everyone knows that lightweight construction reduces product weight, saves on materials and reduces production costs. But what most people don't know is that that's just the beginning – and therein lies the challenge. Because the real point of lightweight is that it makes products and components better by enhancing durability, improving efficiency and paving the way to better design. What's more, it makes for more efficient use of resources and materials and reduces energy consumption and hence emissions. All of which increases competitiveness while helping to combat climate change. "Lightweight construction will be a very important topic at HANNOVER MESSE 2019," commented Olaf Daebler, Deutsche Messe's Global Director Industrial Supply for HANNOVER MESSE. "Users from all industries will find experts who will show them how they can use lightweight construction to enhance their products." With numerous companies and industry associations showcasing intelligent lightweight solutions at all sections of HANNOVER MESSE, there will certainly be no shortage of quality information on offer. And the central headquarters of it all will be Hall 5 at the Industrial Supply show. "Rapid growth in urban infrastructure, digitization, increasing mobility and burgeoning industrial production are all putting enormous pressure on finite natural resources," says Dr. Elmar Witten, CEO of Germany's Federation of Reinforced Plastics (AVK). "So, to conserve these resources and safeguard our energy supply, we need to find new approaches. Fiber-reinforced plastics/composites offer excellent solutions for many of these challenges, because, as construction materials, they differ fundamentally from unreinforced and metallic materials. Unfortunately, it still tends to be only materials specialists who know about them. That is why we are again partnering with HANNOVER MESSE – to raise awareness of these outstanding materials." At the upcoming HANNOVER MESSE, technology users will be able to gain a quick yet impressively comprehensive overview of the many lightweight material groups and applications available to them. This includes both general and tailored information. The following HANNOVER MESSE events and group presentations will deal with lightweight construction this April: 1 Lightweighting Summit: In 2019, the German Economics Ministry is organizing HANNOVER MESSE's first-ever summit on lightweight construction . The summit for political, industry and R&D leaders, which will be held on 2 April, will look at lightweight design and construction as a competitive factor and explore strategies for fostering it as a key enabling technology. Germany's Federal Minister for Economic Affairs, Peter Altmaier, will give the opening address. Integrated Lightweight Plaza and forum: Located in Hall 5, the Integrated Lightweight Plaza is HANNOVER MESSE's central information hub and marketplace for lightweight solutions across all materials, processes and industries. For companies, business networks, industry associations and research institutions, the plaza is a chance to demonstrate that developing effective lightweight solutions requires interdisciplinary cooperation on materials, design and production technologies. The Integrated Lightweight Plaza comprises an exhibition, a speaker's corner, a ‘Lightweight Café' and a demonstration area. And in an exciting new development, next year's plaza will be run with support from the German Engineering Federation (VDMA). The federation's Working Group on Hybrid Lightweight Technologies, which is tasked with facilitating dialogue between users, suppliers and R&D, is organizing a special showcase at the plaza that will be themed "Lightweight as an Enabler of Tomorrow's Mobility" and which will feature lightweight demonstration displays. The working group is also organizing a companion lightweight-themed program that will run on 2 April 2019 at the Industrial Supply Forum. "Lightweighting in Baden-Württemberg" pavilion At the "Lightweighting in Baden-Württemberg" group pavilion, companies from the German state of Baden-Württemberg will showcase their know-how and solutions in a range of areas, including lightweight core materials for sandwich-construction components, precision cogwheels and gear components made of plastics, and innovative combinations of hand forging and 3D metal printing. The participating companies belong to a local lightweight network named "Leichtbau BW". The highlights of the pavilion include a special exhibition of the ILO 1 lightweight concept car. The companies in the "Leichtbau BW" network jointly developed the vehicle from start to finish in the space of just four months, a feat made possible by a web-based PLM system that enabled them to efficiently allocate and coordinate all the various production, development and engineering design tasks involved. The ILO 1 is also jam-packed with lightweight tech. It had to be: in order to keep its rating as a L7e lightweight electric vehicle, the whole unit, minus battery, had to weigh no more than 450 kg. "For visitors, the ILO 1 is a tangible embodiment of the two main theme areas that intersect in Hall 5 – Lightweight Construction and Digital Factory," commented Leichtbau BW GmbH CEO Dr. Wolfgang Seeliger. Group pavilion by Landshut Cluster for Lightweight Design Transitioning business ideas into market-ready products and services is very much a matter of collaboration, particularly when the companies in question are at the SME end of the size spectrum. The Cluster for Lightweight Design is a prime example of this. It is a network of SMEs, service providers and research institutions, spearheaded by Landshut University of Applied Sciences. And 2019 will be the ninth year in a row that the cluster has run a group pavilion at HANNOVER MESSE. "Within HANNOVER MESSE, the Lightweight Construction display area gives visitors access to an unparalleled concentration of expertise for their lightweight technology projects," said Marc Bicker, Commercial and Organisational Director of the Landshut Cluster for Lightweight Design. "At the group pavilion, representatives of companies and universities will present and discuss the latest developments in the highly innovative and interdisciplinary field of lightweight design." In 2019, the organizers of HANNOVER MESSE will again also be putting out a Lightweight Construction Guide – a publication that helps visitors find each of many organizations dotted throughout the venue that offer solutions for or relating to lightweight construction. There will also be a daily Guided Tour of HANNOVER MESSE themed "Lightweight Technologies in Industrial Applications". The tour is new to the trade show's lightweight line-up.
Eccrine Systems, Inc., an advanced sweat sensor company, today announced that a key patent, US10136831, has been issued to Dr. Jason Heikenfeld, Co-Founder & CSO, and prominent University of Cincinnati researcher. The company holds exclusive rights to the UC patent. he patented invention covers the use of on-body sweat devices that are capable of electronically correlating two or more measurements of an analyte with the time at which the analyte emerged in newly excreted sweat. Without the use of the invention it is likely not possible to correlate sweat analyte data trends with chronological blood values or similar physiological measurements. Heikenfeld developed his invention over four years ago at a time when continuous on-body measurement of sweat analytes was at its inception. Heikenfeld is a well-known scientific leader of the wearable sweat sensor space with many of its most prescient and important advances to his credit. The company uses Heikenfeld's invention to time correlate the data derived from its sweat sensor devices, including data and algorithms that will define the pharmacokinetic (PK) profile of medications that are excreted in locally stimulated sweat. "Non-invasive medication monitoring is a great example of the utility of Jason's invention," says Dr. Gavi Begtrup, CEO of Eccrine Systems. "You can't devise an on-body device to derive a sweat pharmacokinetic curve, and then correlate that curve to a drug's blood PK curve, without using this invention. This is a big deal given the estimated $500 billion dollar annual healthcare cost of non-optimized medication therapy, a significant portion of which can result from individual PK differences that cause failed treatment outcomes."
Researchers then use DNA- and RNA- sequencing to look at populations of cells, examining which genes are expressed within a sample of cancerous tissue. However, traditional sequencing methods can hide that fact that not all tumor cells necessarily behave in the same way. Not recognizing this means that if you target a tumor with a specific type of drug, some cells may be just different enough to survive and thrive. In a major advance for genomics, it is now possible to look at what one single cell is doing at any given time with a technique called single-cell RNA sequencing (scRNA-seq). This method looks at the amount of messenger RNAs (mRNAs) in a cell and compares those to other cells to look for differences in gene expression. However, what information you find can depend on how your run your experiment and how the data are analyzed. Lana Garmire, Ph.D., associate professor of the department of computational medicine & bioinformatics at Michigan Medicine and her team is studying ways to eliminate some of the biases that can make interpreting scRNA-seq data difficult. "A lot of the noise in this type of sequencing comes from the fact that you have to measure samples in extreme low quantities and in different batches," she explains. Differences that arise due to this split are called batch effects. Genomics researchers must correct for these batch effects, but this process can raise a conundrum: how do you know if a difference is a batch effect or a true difference between cells? Bioinformatics is the term for collecting and analyzing complex biological data using computer programs. It is a relatively new field born out of the ability to gather enormous amounts of biological data, such as DNA and protein sequences. Researchers rely on bioinformatics techniques to determine which genes are expressed in single cells. But they've had to work around the noise introduced through different research protocols and batch effects. Garmire, who recently joined U-M from the University of Hawaii and is the new faculty director University of Michigan Medical School Bioinformatics Core, has discovered a more efficient way of identifying differences between cells using the same set of data produced during sequencing experiments. Instead of relying on gene expression, she found that looking at what are known as single nucleotide variants (SNVs) can eliminate some of this uncertainty. "With SNVs, you are dealing with numbers that are binary, 0 and 1. Either the mutation is there or not." Recall that genes are made up of nucleotides represented by the letters A, T, G and C that make up a code that is translated into a protein. Garmire's method looks for differences in single nucleotides, knowing that an A can only be replaced by a T and a G by a C. This new work, described in Nature Communications, developed a new set of procedures to process scRNA-seq data and retrieve this variant information. Further, using a computer program called SSrGE, they can link this variant information to more traditional gene expression information. "This gives us information on different subpopulations of tumor cells and becomes sort of like a fingerprint that can be marked to identify cell-to-cell differences," says Garmire. Ultimately, drug makers and clinicians use these targets to guide pharmaceutical treatments. "When you want to attack the issue, you go at it by attacking the fundamental features of that issue: the mutations. Clinicians may be able to use this information later on to guide their therapeutics." Garmire looks forward to bringing bioinformatics out of the lab, helping researchers who amass large amounts of data to use them and develop downstream clinical applications. "We divide the body up and specialize but at the end of the day, you need to look holistically and ask, what am I doing and who is this helping?
Contrary to some analyses, according to which German medium-sized enterprises have missed the boat on digitization , a recent study by the consultancy company PAC and the business software provider proALPHA paints a much more positive picture. It is based on a survey of 102 leading IT and departmental managers from the manufacturing industry. This indicates that 71% have at least undertaken initial pilot projects in the context of Industry 4.0. For 90%, implementation of an ERP system is regarded as the basis for successful digitization. However, more than half criticized existing solutions for being too rigid to allow customized process optimization. Of those surveyed, 62% are therefore planning to modernize their existing ERP solutions and have already taken this into account in their budget planning. As other factors connected with successful digital transformation, 89% cite interdepartmental collaboration, 82% mention training and internal staff development, and 82% support from the highest management level. Another striking aspect of the study, which is free to download , is that although digitization of production is well advanced, there is a lack of consistency in the development of additional digital products and services.
The study targeted people aged 60-69 years, and just under a half of the age group, or a little more than 300,000 people, were randomised by late 2011. Half of the population in the study were invited for screening, while the other half of the age cohort served as a control group. Faecal occult blood tests (FOBT) were used in the screening, and patients who tested positive for blood were referred for a colonoscopy. The first study based on the screening results indicated no significant decrease in mortality, so the screenings were discontinued after 2016. However, researchers from the Helsinki University Hospital and the Finnish Cancer Registry wanted to examine whether the screening had offered benefits to patients with colorectal cancer. "Practically no cancer screenings have been found to have an impact on overall mortality. However, they may still be useful in other ways. We wanted to study whether the patients could avoid the more intense treatments if they participated in screening for colorectal cancer," says Dr. Laura Koskenvuo, gastrointestinal surgeon. The study examined the data of approximately 1,400 patients diagnosed with colorectal cancer. The results indicated that among patients from the screening group, the surgical removal of the entire tumour was more commonly successful than it was among the control group patients, and they were less likely to require chemotherapy. The patients from the screening group were also less likely to undergo emergency surgery because of their tumour than the control group patients. "The control group had 50% more emergency surgeries, 40% more incomplete tumour removals and 20% more chemotherapy treatments than patients in the screening group," says Adjunct Prof. Ville Sallinen, gastrointestinal surgeon. Closer inspection of the results showed that these benefits were particularly prevalent among male patients. Similar benefits were not seen among women. Additionally, the researchers found that the screening was most efficient at detecting left-sided colorectal cancer and the screening was found to have no benefit for patients with cancer on the right side, possibly because blood seeping from tumours on the right side becomes so diluted as it travels through the colon that the gFOBT can no longer detect it. "The strength of this Finnish study is that it randomised an enormous number of people in the public health care system, which meant that we could objectively evaluate the benefits of the screening. Similar studies have not been available anywhere else," says Professor Nea Malila, director of the Finnish Cancer Registry. "In the future, we must examine whether different screening techniques could improve the situation of female patients and facilitate the diagnosis of right-sided colorectal cancer," the researchers state.
When used in industrial fans, radial impellers are exposed to high mechanical, thermal and medial loads. They are usually made of metal. At the Institute of Lightweight Engineering and Polymer Technology (ILK) of TU Dresden, researchers have now developed a radial fan impeller with a modular metal-fiber composite design . Because of its low mass, the load is significantly lower than with metal fan impellers. For the same reason and thanks to the high strength of the composite fiber material, scientists have been able to increase the speed of the impellers significantly. In initial centrifuging tests at the ILK, at a maximum rotational speed of 10,266 rpm a circumferential speed of 543 m/s was achieved – about twice as fast as the maximum speed of a comparable metal impeller. The researchers also point out that, with modern metal-fiber composite designs, fan impellers with multiple parts can be made, which cuts manufacturing costs and simplifies maintenance. The project team around Prof. Maik Gude was awarded the AVK Innovation Prize by the Industrievereinigung Verstärkte Kunststoffe (Industrial Association for Reinforced Plastics) for the development at the International Composites Congress 2018 in Stuttgart.