"We compared three novel tau-specific radiopharmaceuticals – 11C-RO-963, 11C-RO-643, and 18F-RO-948 – that showed pre-clinical in vitro and in vivo promise for use in imaging human tau (Honer et al., JNM, April 2018)," explains Dean F. Wong, MD, PhD, Johns Hopkins University professor of radiology, neurology, psychiatry and neurosciences and director of the Division of Nuclear Medicine's Section of High Resolution Brain PET Imaging. In this first human evaluation of these novel radiotracers, healthy humans and patients with Alzheimer's disease (AD) were studied using an innovative study design to perform head-to-head comparisons of the three compounds in a pairwise fashion. Wong states, "This design allowed us to select one radioligand, 18F-R0-948, as the most promising second-generation tau radiopharmaceutical for larger scale use in human PET tau imaging." Over all brain regions and subjects, the trend was for 18F-RO-948 to have the highest standardized uptake value (SUVpeak), followed by 11C-RO-963 and then 11C-RO-643. Regional analysis of SUV ratio and total distribution volume for 11C-RO-643 and 18F-RO-948 clearly discriminated the AD group from the healthy control groups. Compartmental modeling confirmed that 11C-RO-643 had lower brain entry than either 11C-RO-963 or 18F-RO-948 and that 18F-RO-948 showed better contrast between areas of high versus low tau accumulation. Subsequent analysis therefore focused on 18F-RO-948. Both voxelwise and region-based analysis of 18F-RO-948 binding in healthy controls versus AD subjects revealed multiple areas where AD subjects significantly differed from healthy controls. Voxelwise analysis also revealed a set of symmetric clusters where AD subjects had higher binding than healthy controls. "Importantly, this new tracer appears to have much less off-target binding than was reported for existing tau tracers," notes Wong. "Especially, it has less binding to the choroid plexus adjacent to the hippocampus, which has confounded interpretation of mesial temporal tau measured by first generation PET Tau tracers." He points out, "The significance of this research and the companion research reported in Kuwabara et al. in this same issue is that they describe in detail the selection and quantification of a second-generation tau PET imaging as a complement to amyloid imaging, allowing us to accurately measure tau pathology in living people and contributing to our understanding of the pathophysiology of Alzheimer's and related dementias. Better Tau PET radiopharmaceuticals also provide the promise of improved target engagement and monitoring of anti-tau treatments in future Alzheimer's clinical trials." Collaboration has been key to this research process. Wong emphasizes, "These findings demonstrate the impact of the complementary strengths of preclinical, translational and clinical research with university PET and memory experts, NIH aging experts and dedicated imaging neuroscientists in the pharmaceutical industry to approach one of the greatest global public health challenges–i.e., Alzheimer's disease, where there is still no definitive cure. Improved biomarkers such as PET imaging of tau and, in the future, other dementia-implicated proteins are vital to reducing the enormous costs of drug development and eventually understanding and treating Alzheimer's."
The research, published in Nature Communications, will help in diagnosing disease and, in future, guiding therapeutic intervention. Each cell in our organism has a roughly 2-meter-long molecule of DNA – our genetic information – that needs to be properly packed inside a few micron nucleus. How the DNA is organised in the nucleus is known to play a key role for normal cellular development and function, since mutations in the mechanisms that control this process lead to developmental disorders or diseases such as cancer. However, the exact role that the organisation of the genome plays in disease is currently unknown, since scientists have lacked the ability to thoroughly examine the 3D organisation of the genome in diseased cells. In this new research, scientists have performed a proof-of-principle study demonstrating that the 3D genome can be directly examined in diseased cells from patients. Subtle improvements implemented in this new technique to measure three-dimensional genome architecture, called Low-C, allowed researchers to lower the amount of biological material initially required to perform the experiments. This enabled them to determine the spatial architecture of a diffuse large B-cell lymphoma genome. “To be able to examine the genome architecture of the specific cells that cause disease is really exciting, since currently we do not know how the 3D genome is altered in these cells”, says Dr Noelia Díaz, a postdoctoral fellow in the Vaquerizas Laboratory who led the experimental part of the project. The researchers then performed an advanced computational analysis of the data that revealed some surprising observations. First, the scientists were able to detect genome rearrangements – changes in the normal sequence arrangement of our genome that are a key feature of many cancers – and detected both novel and known translocations characteristic of the disease, which were then experimentally validated. “It was reassuring to see our computational predictions validated experimentally”, says Dr Kai Kruse, a postdoctoral fellow in the Vaquerizas Laboratory who performed the computational analysis of the data. But the data held more surprises. When the researchers examined a finer level of chromatin organisation into topological domains (short sections of the genome that are folded into compact knots resembling balls of yarn), they observed that new domains were present in disease cells in regions of the genome that would otherwise present no domains in healthy cells. “This was a surprising finding, since the 3D architecture of fully developed cells is thought to be rather invariant”, says Dr Juanma Vaquerizas, a Group Leader at the Max Planck Institute for Molecular Biomedicine in Muenster, who supervised the research. “We could observe that these new structural domains appear in regions that contain genes previously known to be associated with cancer and disease, but the functional role of these new domains is currently unknown”, says Vaquerizas. The researchers aim now to extend their studies to more samples, to be able to determine the impact that changes in the 3D structure of the genome play in disease and to use this information in the design of personalised patient-specific treatment options.
Since 2013, the Massive Lightweight Construction initiative has brought together many steel and massive forming companies to develop ideas that reduce the weight of chassis, powertrain, transmission and drive-related electronics in today's vehicles. In the now completed Phase III, the 39 international cooperative project partners applied their ideas to a hybrid 4-wheel drive SUV with a split-axial drive. They dismantled the vehicle and documented its individual parts. The reference mass for the chassis, powertrain, transmission and drive electronics was 816 kg and it was reduced by 93 kg in the course of the research. In a second project, a truck's transmission, cardan shaft and rear axle weighing a total of 909 kilograms were dismantled. In this case the mass was reduced by 124 kilograms. Documentation on the two projects can be downloaded for free on the initiative's website.
The muscle is a highly ordered and hierarchically structured organ. This is reflected not only in the parallel bundling of muscle fibres, but also in the structure of individual cells. The myofibrils responsible for contraction consist of hundreds of identically structured units connected one after another. This orderly structure determines the force which is exerted and the strength of the muscle. Inflammatory or degenerative diseases or cancer can lead to a chronic restructuring of this architecture, causing scarring, stiffening or branching of muscle fibres and resulting in a dramatic reduction in muscular function. Although such changes in muscular morphology can already be tracked using non-invasive multiphoton microscopy, it has not yet been possible to assess muscle strength accurately on the basis of imaging alone. Researchers from the Chair of Medical Biotechnology have now developed a system that allows muscular weakness caused by structural changes to be measured at the same time as optically assessing muscular architecture. "We engineered a miniaturized biomechatronics system and integrated it into a multiphoton microscope, allowing us to directly assess the strength and elasticity of individual muscle fibres at the same time as recording structural anomalies," explains Prof. Oliver Friedrich. In order to prove the muscle's ability to contract, the researchers dipped the muscle cells into solutions with increasing concentrations of free calcium ions. Calcium is also responsible for triggering muscle contractions in humans and animals. The viscoelasticity of the fibres was also measured, by stretching them little by little. A highly-sensitive detector recorded mechanical resistance exercised by the muscle fibres clamped on the device. The technology developed by researchers at FAU is, however, merely the first step towards being able to diagnose muscle disorders much more easily in future: "Being able to measure isometric strength and passive viscoelasticity at the same time as visually showing the morphometry of muscle cells has enabled us, for the first time, to obtain direct structure-function data pairs", Oliver Friedrich says. "This allows us to establish significant linear correlations between the structure and function of muscles at the single fibre level." The datapool will be used in future to reliably predict forces and biomechanical performances in skeletal muscle exclusively using optical assessments based on SHG images (the initials stand for Second Harmonic Generation and refer to images created using lasers at second harmonic frequency), without the need for complex strength measurements. At present, muscle cells still have to be removed from the body before they can be examined using a multiphoton microscope. However, it is plausible that this may become superfluous in future if the necessary technology can continue to be miniaturized, making it possible for muscle function to be examined, for example, using a micro-endoscope.
"If the positive preliminary findings are maintained as the patients enrolled in the study continue to be monitored, that will serve as a strong indication of the promise of cryotherapy as an alternative treatment for a specific group of breast cancer patients," said study lead author Kenneth R. Tomkovich, M.D., radiologist at Princeton Radiology and director of Breast Imaging and Interventions at CentraState Medical Center in Freehold, N.J. Cryoablation, also known as cryotherapy, has been used to treat cancers in other organs in the body, including the kidneys and lungs, but has yet to become an established treatment for breast cancer. Dr. Tomkovich began studying it for that indication more than 10 years ago, as imaging advances in mammography and ultrasound and the development of tomosynthesis enabled the detection of more low-risk cancers. These small, early-stage cancers have the potential to become invasive and life-threatening without treatment. But treatment options have not kept pace with imaging advances. "We're finding smaller and smaller breast cancers, but we're still treating them the same way we did 30 years ago," Dr. Tomkovich said. Cryoablation represents a potential new weapon in the arsenal against breast cancer. The procedure begins with the introduction of a probe into the tumor through a pea-sized incision in the skin while the patient is under local anesthesia. The probe is guided by high-definition ultrasound in conjunction with mammography images. Once the probe is in place, liquid nitrogen is introduced into it. During the initial, eight-minute freeze cycle, an ice ball forms around the tumor, killing the cancer. After a thaw cycle, another eight-minute freeze cycle is used to ensure complete destruction of the cancer cells. The procedure takes less than an hour, and patients are able to return to their normal activities shortly thereafter. As part of the Ice 3 Trial, Dr. Tomkovich and colleagues at 18 centers across the U.S. have been studying cryoablation as a primary treatment for breast cancer without surgical lumpectomy. Starting in 2014, the researchers began performing cryoablation on women ages 60 and over with biopsy-proven, low-risk breast cancer. The patients undergo the procedure and then are followed for recurrence with mammography at six and 12 months and then annually for five years. As of now, the researchers have three-year follow-up data on about 20 patients and two-year follow-up data on more than 75 patients. The preliminary results have been very promising. The procedure was successfully completed in all patients, and no serious adverse events have been reported. Only one patient experienced a recurrence, giving the procedure a 99.4 percent success rate so far. "Lumpectomy is 90 to 95 percent effective at removing cancer," Dr. Tomkovich said. "We were going for something close to that, but our preliminary results have been even better. We're getting the same results at 18 centers around the country." Cryoablation has advantages over ablation techniques that use heat to destroy tumors. For one, tissue retains its appearance when frozen, while heating tends to deform it, making imaging less reliable. Dr. Tomkovich likens the process to how bacon keeps its shape when frozen but curls up and shrinks when cooked. In addition, there is preliminary evidence from studies on mice that cryoablation can stimulate an immune system response against cancer cells in the body. Final results of the study will be published when five-year follow-up data is available for all the women who were treated. "If it's proven that cryoablation works, then some women might be more inclined to opt for it over surgery," Dr. Tomkovich said.
Picking up different objects from a box – bin picking – is one of the hardest tasks for robot or cobot arms. One problem is recognising the objects reliably; another is the great effort needed to train the robot to cope with the different shapes. The Munich company Robominds has now developed a system that helps robots recognize objects automatically and grip them at the right points, without any programming. Robobrain-Vision is a bin-picking solution that consists of a 3D stereo camera and AI software that runs on a powerful computer. The camera takes high-resolution images of the work area, and the software then determines the gripping points of the unsorted workpieces. The material, shape and surface do not matter and the items can even overlap. The system can also deal with varying lighting conditions. Interaction with a cobot from the market leader Universal Robots works via a UR plug-in. Interfaces also make the system compatible with other robots and cobots, such as those made by Kuka and Franka. Robominds sees the logistics industry as the most important area of application.
The initiative of the Swiss energy and automation company ABB focuses on European start-ups. They are invited to present and develop their AI solutions for use in a wide range of areas in which ABB operates, from industrial automation, through to robotics and power grids, to smart cities and buildings. Up to ten start-ups will be selected and will work together with ABB business units on sample applications and core industrial challenges. At the same time, they are given coaching, technical support and the opportunity to acquire new customers and commercialize their solutions at a global level. The most successful start-up wins a prize at the end of the program. ABB Technology Ventures (ATV), the strategic venture capital unit of ABB, is responsible for networking within the company. The program is supported by the Berlin high-tech accelerator and business intelligence provider AtomLeap .
altAirnative GmbH from Mühlhausen in Thuringia has developed a new process for energy-efficient production of compressed air. While other companies usually construct a cogeneration plant to drive compressors with the electricity it generates, the founders of altAirnative use compressed air heating and power stations in which a combustion engine run on natural gas supplies the compressors. The advantage: there are hardly any efficiency losses in this process, as the heat generated is exploited almost entirely. The prototype for the compressed air heating and power station was first presented two years ago. Six different models are now available, from the small D-Föhn to the large D-Tornado with an output of 300 kW. According to the manufacturer, the machines, which sell from around EUR 100,000, pay for themselves in from two to four years. The systems are adapted to the customer’s requirements by altAirnative. The company has high hopes for the Italian and UK markets, where large volumes of compressed air are required there and the difference between electricity and gas prices is particularly large.
The Japanese semi-conductor company Renesas Electronics has developed an embedded controller for energy harvesting, based on proprietary SOTB (silicon on thin buried oxide) technology. The R7F0E is a 32-bit embedded controller based on an arm cortex with up to 64 MHz cycle frequency for fast local processing of sensor data and for analytical and control functions. With 20 μA/MHz in active mode and a deep standby current of 150 nA, the R7F0E is suitable for energy saving and energy harvesting applications. It allows direct connection to ambient energy sources, such as solar energy and vibration. As a result, system manufacturers are able to eliminate batteries in some of their products. In addition, EnOcean , the specialist in energy harvesting from Oberhaching near Munich, has introduced the “Battery-free by EnOcean” seal for maintenance-free and flexible circuit solutions that work without batteries and cables. Product manufacturers can now use the new logo to advertise their battery-free wireless circuits that integrate the EnOcean technology for leading wireless standards in the sub-1GHz and 2.4 GHz range.
The portable innovation, which resembles a stethoscope, is made up of an acoustic sensor connected to a smartphone. It enables early intervention by allowing patients to check for excess fluid in the lungs at home. Fluid accumulation in the lungs, which causes breathlessness, is a common symptom of congestive heart failure. One in five people worldwide run the risk of developing congestive heart failure, and this prevalence increases with age. As there is no cure for the ailment, patients can only monitor their health closely with lifestyle changes or medication to prevent their heart function from deteriorating irreversibly. Currently, patients can only check for fluid accumulation in the lungs by going for a clinical examination, which can be considerably subjective, or through imaging modalities and serum biomarker tests, which are costly and take a longer time. The non-invasive device built by a team led by NTU Associate Professor Ser Wee and TTSH Associate Professor David Foo circumvents these problems with its portability, ease of use and quick results. Currently a prototype, the device is able to detect any excess fluid in the lungs in 10 seconds once placed on the patient's chest or back. In a pilot study using lung sounds recorded from TTSH's congestive heart failure patients, Assoc Prof Ser and his team found the device to have over 92 per cent accuracy in identifying patients with the condition - comparable to existing 'gold standard' diagnosis methods such as X-rays and CT scans. The findings were first presented at the 2012 Annual International Conference of the IEEE Engineering in Medicine and Biology Society. Associate Professor Foo, Head of Cardiology at TTSH, said, "Patients can monitor their condition at home and use the device whenever they feel slightly breathless at home. It is potentially a game-changer in the management of ambulatory heart failure patients. It can also provide a rapid and accurate acute diagnosis of heart failure in situations of undifferentiated shortness of breath symptoms." Associate Professor Ser from NTU's School of Electrical and Electronic Engineering added, "Currently, such diagnosis can only be conducted through clinical examination, which cannot be made frequently. Our smart medical device can be used by anyone, anywhere and any number of times, which will enable the possibility of early intervention of congestive heart failure. "The next wave of MedTech (medical technology) start-ups will see the massive proliferation of smart medical devices that rely on artificial intelligence (AI) and sensing technologies, such as the one we invented, and that will enable personalised self-assessment and screening of cardiopulmonary and other diseases, and revolutionise the way healthcare is managed in future." In congestive heart failure, the diseased or overworked heart ventricle is unable to pump out enough of the blood it receives from the lungs. This causes pressure to build up first in the heart, then in the veins and capillaries in the lungs. The pressure then pushes fluid back through the capillary walls and into the air sacs of the lungs. As a result, when air passes through these fluid-filled air sacs, crackles can be heard from the lungs. Based on this principle, Prof Ser and his team found a unique set of features that can be used to identify characteristics of sounds unique to patients with fluid accumulation in the lungs. They then developed a proprietary AI algorithm capable of identifying and processing these signals to determine if there is fluid accumulation in the lungs. The smart medical device developed by NTU and TTSH first picks up breathing sounds through a sound sensor. Through a mobile app, the sound signals are then sent to a server located in the cloud. The NTU-developed algorithm stored in the cloud then processes these sound signals, and the results are shown on the mobile app. This whole process takes about 10 seconds to complete.