The term 'PUVA' stands for 'psoralen' and 'UV-A radiation'. Psoralens are natural plant-based compounds that can be extracted from umbelliferous plants such as giant hogweeds. Plant extracts containing psoralens were already used in Ancient Egypt for the treatment of skin diseases. Modern medical use began in the 1950s. From then on, they were applied for light-dependent treatment of skin diseases such as psoriasis and vitiligo. From the 1970s onwards, PUVA therapy was used to treat a type of skin cancer known as cutaneous T-cell lymphoma. Psoralens insert between the crucial building blocks (bases) of DNA, the hereditary molecule. When subjected to UV radiation, they bind to thymine -- a specific DNA base -- and thus cause irreversible damage to the hereditary molecule. This in turn triggers programmed cell death, ultimately destroying the diseased cell. Researchers working with Prof. Dr. Peter Gilch from HHU's Institute of Physical Chemistry have now collaborated with Prof. Dr. Wolfgang Zinth's work group from LMU Munich to analyse the precise mechanism of this binding reaction. They used time-resolved laser spectroscopy for this purpose. They found that -- after the psoralen molecule has absorbed UV light -- the reaction takes place in two stages. First, a single bond between the psoralen molecule and thymine forms. A second bond formation then yields a four-membered ring (cyclobutane) permanently connecting the two moieties. The researchers in Düsseldorf and Munich were also able to demonstrate that the first stage takes place within a microsecond, while the second needs around 50 microseconds. They compared this process with the damaging of the 'naked' DNA by UV light. That process also frequently results in cyclobutane rings, but the process takes place considerably faster than when psoralens are present. Prof. Gilch explains the background to the research: "If we can understand how the reactions take place in detail, we can change the psoralens chemically in a targeted way to make PUVA therapy even more effective." Together with his colleague in organic chemistry, Prof. Dr. Thomas Müller, he wants to develop these high-performance psoralen molecules at HHU within the scope of a DFG project.
The future IoT will put much higher demands on data rates, reliability and latency of wireless connections. If many future IoT devices communicate in a small space, the need for transmission frequencies will increase much faster than previously thought. With LiFi, ELIoT introduces a new, networked wireless communication technology that works in the previously unused spectrum of light, in addition to WiFi and mobile radio. LiFi allows many applications for commercial, industrial or outdoor applications. It could be used successfully in environments where radio frequencies can not or should not be used. For outdoor use, it could enable high-bandwidth, direct-from-roof to roof-to-roof connections, between street lights or to consumers' homes in the next-generation network. Higher demands on wireless networks are likely to be due to software-controlled production (Industry 4.0), virtual and augmented reality, and autonomous driving. Also for LiFi could be used. ELIoT started in 2019 as part of the EU's largest research and innovation program, Horizon 2020. This program is designed to deliver groundbreaking results by bringing good ideas from the lab to market. ELIoT receives EUR 6 million in funding from the public-private partnership "Photonics21". Partners include Signify (formerly Philips Lighting), Nokia, MaxLinear, Deutsche Telekom, KPN, Weidmüller, LightBee, Oxford University, Eindhoven University of Technology and the two Fraunhofer Institutes Heinrich Hertz Institute HHI and FOKUS. Other companies will soon follow as associated partners. "With ELIoT, we have established an extremely efficient consortium of companies and organizations in the European lighting and communications industries. ELIoT is building a closed value chain with partners working with research facilities on components, chipsets, systems, and applications to make LiFi technology commercially viable for the IoT of the future, "says Project Coordinator Dr. Ing. Volker Jungnickel (Fraunhofer HHI). Prof. Jean-Paul Linnartz, co-initiator of ELIoT and head of LiFi research at Signify, highlights the potential of ELIoT: "LiFi offers interference-free high-speed, high-reliability communication. The available bandwidth can be fully reused in each room. The lighting infrastructure provides a great way to wirelessly network the rapidly growing number of devices. "
Measurement technology is currently not capable of efficiently and fully measuring the temperatures in an electric motor – the necessary sensors and their installation are simply too expensive. Temperatures in the rotating parts are particularly difficult to measure. The problem, however, is not only the lack of measuring instruments, but also the deviations that can occur during mass production. That is why manufacturers must provide for additional safety reserves, which in turn reduce the efficiency of the motors. As part of a project funded by the German Research Foundation (DFG), scientists from the Department of Power Electronics and Electrical Drive Technology at the University of Paderborn now aim to develop software capable of estimating the temperatures at certain points. In doing so, they are paying special attention to the sensitive and expensive permanent magnets. The researchers are looking for the solution in data-driven approaches. They are making use of artificial intelligence and machine learning to find new models for estimating the temperature in drives and other power engineering applications. This involves training their software with black-box approaches and experimental test-bench measurements in order to obtain the most precise temperature estimates possible.
Damaged DNA inside cells can lead to the development of cancer, neurodegenerative disorders and many other diseases. To fix the problem, organisms have evolved to rapidly tag a number of ‘repair proteins’ near the site of damage with chemical flags. This process, known as ADP-ribosylation (ADPr), acts like an alarm system to identify the place where help is needed. So fundamental is ADPr to understanding how cells deal with DNA damage that some chemotherapy drugs, which have been designed to prevent key enzymes involved in the process from working, are already being used to treat certain types of breast, ovarian and prostate cancers. Yet the underlying molecular mechanisms of ADPr are still poorly understood – something that is limiting our ability to develop new, more effective treatments. It was already known that ADPr flags attach to particular sites on proteins within damaged cells, but it was unclear exactly where. More recent studies have shown that ADPr flags attach to a number of amino acids – the building blocks of proteins. The original aim of the EU-funded INVIVO_DDR_ADPR project was to map all the amino acid sites for ADPr flags in the worm Caenorhabditis elegans – an undertaking that promised to fully reveal the molecular mechanisms for repairing damaged DNA. But after the first set of experiments, the researchers discovered that ADPr flags can also attach to the amino acid serine. Overlooked for 50 years, this is an incredibly important aspect of the DNA repair process; if scientists can understand the regulatory networks that underlie this complex biological process, it will provide new insights for improved treatment of diseases that relate to DNA damage, including cancer. ‘It may seem like a small detail, but in the cell “factory” this is an important mechanism,’ says researcher Juan José Bonfiglio, from the INVIVO_DDR_ADPR research group co-ordinated by Ivan Matic at the Max Planck Institute for Biology of Ageing in Germany. ‘It’s like discovering a new letter in an alphabet you thought you knew – namely the alphabet the cell uses for sending vital internal messages.’ Improving DNA repair to treat disease? Because this finding was so unexpected, the team altered some of the project’s specific aims to focus on this new discovery. They went on to work out the molecular mechanism by which the ADPr signal is ‘written’ on to the amino acid serine and how it is then erased again. Their work has also shown that the flagging of serine plays a very important role in the cell’s response to DNA damage. The team’s work has the potential to provide important insights for the improved treatment of diseases such as cancer, by opening up new possibilities to improve and increase the efficiency of the DNA repair machinery. New tools for science ‘Our discovery revealed how important discoveries may be hidden in scientific “blind spots”,’ says Bonfiglio, who received funding through the EU’s Marie Skłodowska-Curie fellowship programme for this project. The need to progress their research also forced the team to come up with novel tools, which have led to two patent applications. These include a new, first-instance approach to generating antibodies that are site-specific and enable detection of specific ADPr sites. ‘We’re convinced that these tools will be useful not only for our own projects but for the scientific community in general,’ says Bonfiglio.
Researchers can determine the disease vulnerability of older people using a defined set of substances in the blood Researchers on ageing from the Max Planck Institute for Biology of Ageing and the Leiden University Medical Center (LUMC) collaborate to link basic insights from model organisms to the causes of ageing in humans. They found a combination of biomarkers in the blood which could help estimate the disease vulnerability of elderly people in clinical studies and could possibly be used in intervention studies in model organisms that slow down ageing. When basic researchers investigate the molecular basis of ageing, they usually study model organisms such as worms, fruit flies or mice. The Max Planck Institute for Biology of Ageing aims to link basic insights into ageing to the causes and processes underlying ageing-associated diseases in humans and has therefore recruited Prof. Eline Slagboom from the Leiden University Medical Center in the Netherlands (LUMC) as a Max Planck Fellow in 2018. Now the researchers have identified a set of biomarkers in human blood which could be used in parallel in clinical studies and in ageing research on model organisms. The scientists searched in blood samples of 44,168 individuals for biomarkers that are indicative of a person’s remaining lifespan. After an extensive analysis, the scientists arrived at a set of 14 biomarkers which include for example, various amino acids – the building blocks of proteins – and levels of ‘good’ and ‘bad’ cholesterol, fatty acid balances and inflammation. Clinical studies The blood-based measurement is intended as a first step towards a more personalised treatment of the elderly, explains study director Prof. Eline Slagboom. “As researchers on ageing, we are keen to determine the biological age. The calendar age just doesn’t say very much about the general state of health of elderly people: one 70-year-old is healthy, while another may already be suffering from three diseases. We now have a set of biomarkers which may help to identify vulnerable elderly people, who could subsequently be treated." Model organisms The set of biomarkers is also a starting point for parallel studies in model organisms. “Ageing research in model organisms is ahead of that in humans. To make use of that knowledge we need instruments to compare human and animal studies and this could be one. We are currently investigating if the identified substances can be found in the blood of typical model organisms such as mice and if they are affected by interventions in ageing.”, explains Slagboom. The researchers are now working on answering these questions together with the Cluster of Excellence for Aging Research at the University of Cologne. This large-scale study was possible through collaboration of LUMC with international biobanks, BBMRI-NL (Biobanking and BioMolecular resources Research Infrastructure the Netherlands) and the Max Planck Institute for Biology of Ageing in Cologne. Original publication Joris Deelen, Johannes Kettunen, Krista Fischer, Ashley van der Spek, Stella Trompet, Gabi Kastenmüller, Andy Boyd, Jonas Zierer, Erik B. van den Akker, Mika Ala-Korpela, Najaf Amin, Ayse Demirkan, Mohsen Ghanbari, Diana van Heemst, M. Arfan Ikram, Jan Bert van Klinken, Simon P. Mooijaart, Annette Peters, Veikko Salomaa, Naveed Sattar, Tim D. Spector, Henning Tiemeier, Aswin Verhoeven, Melanie Waldenberger, Peter Würtz, George Davey Smith, Andres Metspalu, Markus Perola, Cristina Menni, Johanna M. Geleijnse, Fotios Drenos, Marian Beekman, J. Wouter Jukema, Cornelia M. van Duijn, P. Eline Slagboom A metabolic profile of all-cause mortality risk identified in an observational study of 44,168 individuals Nature Communications, August 20th, 2019. DOI: 10.1038/s41467-019-11311-9
For 8-million adults who suffer from post-traumatic stress disorder in any given year, medication and cognitive therapy have been the treatment protocol. Now, University of Houston assistant professor of electrical engineering Rose T. Faghih is reporting in Frontiers in Neuroscience that a closed-loop brain stimulator, based on sweat response, can be developed not only for PTSD patients, but also for those who suffer an array of neuropsychiatric disorders. “Sweat primarily helps maintain body temperature; however, tiny bursts of sweat are also released in response to psychologically arousing stimuli. Tracking the associated changes in the conductivity of the skin, which can be seamlessly measured using wearables in real-world settings, thus provides a window into a person’s emotions,” reports Faghih. For people with movement disorders like Parkinson’s disease and essential tremor, who have not responded to medication, application of high-frequency electric current to the brain, or deep brain stimulation, is regarded as most effective. Electrodes are placed in certain areas of the brain to regulate abnormal functions and a pacemaker-like device, placed in the upper chest, controls the amount of stimulation the brain receives. Open-loop stimulators, the most widely-used, deliver continuous stimulation until manually re-adjusted by a physician. Closed-loop stimulators, which provide stimulation in response to biomarkers of pathologic brain activity, have been developed for movement disorders, but are yet to be explored for the treatment of neuropsychiatric disorders. Signaling the onset of a PTSD episode, skin develops the tiniest sheen of perspiration. That symptom of the body’s fight or flight response signals a change in the skin’s electrical conductivity and provides a window into the brain’s state of emotional arousal. Using skin conductance to create the framework for a deep brain stimulator seemed logical to Faghih after reviewing group studies of Vietnam combat veterans with PTSD. Among the findings, PTSD subjects had the largest skin conductance responses when confronted with combat-related words. In a similar study comparing Vietnam combat veterans with and without PTSD and non-combat controls, PTSD veterans had the highest baseline skin conductance levels. “Skin conductance additionally has the advantage of being easily measured with wearable devices that afford convenience, seamless integration into clothing and do not involve risk of surgically implanted sensors,” said Faghih. The ultimate goal will be to develop closed-loop prototypes that can eventually be used for treating patients in a variety of neuropsychiatric disorders. Faghih’s graduate researchers Dilranjan Wickramasuriya and Md. Rafiul Amin were first and second authors, respectively, of the article. This project was supported, in part, by a grant from the National Science Foundation.
A novel neck brace, which supports the neck during its natural motion, was designed by Columbia engineers. This is the first device shown to dramatically assist patients suffering from Amyotrophic Lateral Sclerosis (ALS) in holding their heads and actively supporting them during range of motion. This advance would result in improved quality of life for patients, not only in improving eye contact during conversation, but also in facilitating the use of eyes as a joystick to control movements on a computer, much as scientist Stephen Hawkins famously did. A team of engineers and neurologists led by Sunil Agrawal, professor of mechanical engineering and of rehabilitation and regenerative medicine, designed a comfortable and wearable robotic neck brace that incorporates both sensors and actuators to adjust the head posture, restoring roughly 70% of the active range of motion of the human head. Using simultaneous measurement of the motion with sensors on the neck brace and surface electromyography (EMG) of the neck muscles, it also becomes a new diagnostic tool for impaired motion of the head-neck. Their pilot study was published August 7 in the Annals of Clinical and Translational Neurology. The brace also shows promise for clinical use beyond ALS, according to Agrawal, who directs the Robotics and Rehabilitation (ROAR) Laboratory. "The brace would also be useful to modulate rehabilitation for those who have suffered whiplash neck injuries from car accidents or have from poor neck control because of neurological diseases such as cerebral palsy," he said. "To the best of my knowledge, Professor Agrawal and his team have investigated, for the first time, the muscle mechanisms in the neck muscles of patients with ALS. Their neck brace is such an important step in helping patients with ALS, a devastating and rapidly progressive terminal disease," said Hiroshi Mitsumoto, Wesley J. Howe Professor of neurology at the Eleanor and Lou Gehrig ALS Center at Columbia University Irving Medical Center who, along with Jinsy Andrews, assistant professor of neurology, co-led the study with Agrawal. "We have two medications that have been approved, but they only modestly slow down disease progression. Although we cannot cure the disease at this time, we can improve the patient's quality of life by easing the difficult symptoms with the robotic neck brace." Commonly known as Lou Gehrig's disease, ALS is a neurodegenerative disease characterized by progressive loss of muscle functions, leading to paralysis of the limbs and respiratory failure. Dropped head, due to declining neck muscle strength, is a defining feature of the disease. Over the course of their illness, which can range from several months to more than 10 years, patients completely lose mobility of the head, settling in to a chin-on-chest posture that impairs speech, breathing, and swallowing. Current static neck braces become increasingly uncomfortable and ineffective as the disease progresses. To test this new robotic device, the team recruited 11 ALS patients along with 10 healthy, age-matched subjects. The participants in the study were asked to perform single-plane motions of the head-neck that included flexion-extension, lateral bending, and axial rotation. The experiments showed that patients with ALS, even in the very early stages of the disease, use a different strategy of head-neck coordination compared to age-matched healthy subjects. These features are well correlated with clinical ALS scores routinely used by clinicians. The measurements collected by the device can be used clinically to better assess head drop and the ALS disease progression. "In the next phase of our research, we will characterize how active assistance from the neck brace will impact ALS subjects with severe head drop to perform activities of daily life," said Agrawal, who is also a member of Columbia University's Data Science Institute. "For example, they can use their eyes as a joystick to move the head-neck to look at loved ones or objects around them."
The secret to the success of the ArcWorld cells is as simple as it is effective - take one Motoman robot, a positioning system, controller and power source and combine them in one space-saving platform that can be put straight to use. This ensures the robot cells are easy to install and operate and, if necessary, can also be quickly moved to a new location without any difficulty. The two new and most compact members of the product family to date now make these benefits available in even the smallest of spaces. The ArcWorld RS Mini cell needs just 2.3 square meters of clear floor space, and the ArcWorld HS Micro cell as little as 1.4 square meters. Like their big sisters, the two compact cells come with platform, casing, robot, welding kit and all the necessary accessories included. To satisfy all safety standards, the robot and welding kit are completely encapsulated by a polycarbonate glare shield. And, when it comes to the welding kit itself, customers can choose from a number of suppliers, including Kemppi, Esab and Migatronic. Each of the welding kits available includes a welding power source, cable bundle, wire feeder and welding torch. The system robot is the Motoman AR900, which YASKAWA now also manufactures directly in Europe. Besides exhibiting excellent path accuracy, it also boasts an IP67 protection rating and can therefore be used for welding and other automation tasks in even harsh environments – without requiring any additional modifications. A lean and organic design ensures the robot can reach deep into the working areas, while its smooth surfaces make it easy to clean. The AR900 is controlled via a single cable, which again saves space and also reduces wear. What’s more, this ingenious solution promises to drive down the costs associated with maintenance and spare parts inventories.
Scientists have devised a new computational method that reveals genetic patterns in the massive jumble of individual cells in the body. The discovery, published in the journal eLife, will be useful in discerning patterns of gene expression across many kinds of disease, including cancer. Scientists worked out the formulation by testing tissue taken from the testes of mice. Results in hand, they’re already applying the same analysis to biopsies taken from men with unexplained infertility. Don Conrad Ph.D. (2019) Donald Conrad, Ph.D. “There have been very few studies that attempt to find the cause of any disease by comparing single-cell expression measurements from a patient to those of a healthy control. We wanted to demonstrate that we could make sense of this kind of data and pinpoint a patient’s specific defects in unexplained infertility,” said co-senior author Donald Conrad, Ph.D., associate professor and chief of the Division of Genetics in the Oregon National Primate Research Center at Oregon Health & Science University. Simon Myers, Ph.D., of the University of Oxford, also is a senior co-author. Conrad said he expects the new method will advance the field of precision medicine, where individualized treatment can be applied to the specific nuance of each patient’s genetic readout. The scientists made the breakthrough by applying a method recently developed at the University of Oxford to gene expression data from the massive trove of individual cells comprising even minuscule tissue biopsies. The method is known as sparse decomposition of arrays, or SDA. “Rather than clustering groups of cells, SDA identifies components comprising groups of genes that co-vary in expression,” the authors write. The new study applied the method to 57,600 individual cells taken from the testes of five lines of mice: Four that carry known genetic mutations causing defects in sperm production and one with no sign of genetic infertility. Researchers wanted to see whether it was possible to sort this massive dataset based on the variation in physiological traits resulting from differences in the genes expressed in the RNA, or ribonucleic acid, of individual cells. Researchers found they were able to cut through the statistical noise and sort many thousands of cells into 46 genetic groups. “It’s a data-reduction method that allows us to identify sets of genes whose activity goes up and down over subsets of cells,” Conrad said. “What we’re really doing is building a dictionary that describes how genes change at a single-cell level.” The work will immediately apply to male infertility. Infertility affects an estimated 0.5% to 1% of the male population worldwide. Current measures to treat male infertility involve focus on managing defects in the sperm itself, including through in vitro fertilization. However, those techniques don’t work in all cases. “We’re talking about the problem where you don’t make sperm to begin with,” Conrad said. This new technique could open new opportunities to diagnose a specific genetic defect and then potentially rectify it with new gene-editing tools such as CRISPR. Identification of a specific cause would be a vast improvement over the current state of the art in diagnosing male infertility, which amounts to a descriptive analysis of testicular tissue biopsies. “The opportunity provided by CRISPR, coupled to this kind of diagnosis, is really a match made in heaven,” Conrad said. This work was supported by National Institutes of Health grants R01HD078641 and R01MH101810; Wellcome Trust grants 098387/Z/12/Z and 212284/Z/18/Z and 109109/Z/15/Z. Research was further supported by the NIH Office of the Director to the Oregon National Primate Research Center, Award No. P510D011092.
A technology that can obtain high-resolution, micrometer-sized images for mass spectrometric analysis without sample preparation has been developed. DGIST Research Fellow Jae Young Kim and Chair-professor Dae Won Moon’s team succeeded in developing the precise analysis and micrometer-sized imaging of bio samples using a small and inexpensive laser. DGIST announced that Research Fellow Jae Young Kim in the Department of Robotics Engineering and Chair-professor Dae Won Moon’s team developed a technology that can analyze experiment samples without any preparation processing. Due to its ability to obtain high-resolution mass spectrometric images without an experimental environment using ‘continuous wave laser’1, the technology is expected to be applied widely in the precise medicine and medical diagnosis fields. Many advance preparations are needed for the mass spectrometric imaging of biometric samples using ‘specimen,’ which thinly cut an object to analyze. The specimen must be changed artificially since they cannot be analyzed accurately in a room temperature or atmospheric pressure. To develop a convenient analysis technology and ease the burden, Research Fellow Kim started the research. The research team installed a lens carrying continuous wave laser right below a microscope substrate where the specimen is put and shot the laser on it to measure mass spectra by examining molecules from desorption2. The mass spectra can be analyzed through a continuous wave laser whose energy is weaker than other lasers because of the use of ‘graphene substrate’ below the specimen. Since the honeycomb-patterned graphene has very high heat conductivity and can convert light into heat, it can secure enough heat needed for specimen analysis with small amount of light generated by the continuous wave laser. This technology is also advantageous for obtaining high-resolution analysis images, because it can secure space to observe specimen much more closely even when using a 20x magnifying lens. Chair-professor Dae Won Moon in the Department of New Biology explained that “Through this technology, we could greatly shorten the preparation time for analysis by omitting the specimen preprocessing step. Our next plan is to develop the technology further so it can be applied in various areas such as medical diagnosis.” This research was participated by Research Fellow Jae Young Kim in the Department of Robotics Engineering and Ph.D. candidate Heejin Lim in the Department of New Biology as the co-first authors and was conducted with Professor Cheol Song in the Department of Robotics Engineering at DGIST, Professor Dong-Kwon Lim at Korea University, and Research Professor Ji-Won Park at Chungnam National University. The results were published as the cover paper on “ACS Applied Materials & Interfaces,” an international journal in the chemical and nano-technology field, on July 31. 1 Continuous wave laser: Emits laser beam continuously, is smaller and cheaper than pulse-type laser, and has a simple structure. Also referred to as ‘CW laser.’ 2 Desorption: Molecules absorbed on a solid surface fall off from the surface due to heat, light, electronic shock, etc. For more information, contact: Dae Won Moon, Chair Professor Department of New Biology Daegu Gyeongbuk Institute of Science and Technology (DGIST) E-mail: email@example.com Associated Links Research Paper in Journal of ACS Applied Materials & Interfaces https://pubs.acs.org/doi/10.1021/acsami.9b02620 Journal Reference Jae Young Kim, Heejin Lim, Sun Young Lee, Cheol Song, Ji-Won Park, Hyeon Ho Shin, Dong-Kwon Lim, and Dae Won Moon, "Graphene-Coated Glass Substrate for Continuous Wave Laser Desorption and Atmospheric Pressure Mass Spectrometric Imaging of Live Hippocampal Tissue", ACS Applied Materials & Interfaces, Published on July, 2019.