Trigeminal neuralgia: new classification and diagnostic grading for practice and research

Trigeminal neuralgia (TN) is an exemplary condition of neuropathic facial pain. However, formally classifying TN as neuropathic pain based on the grading system of the International Association for the Study of Pain is complicated by the requirement of objective signs confirming an underlying lesion or disease of the somatosensory system. The latest version of the International Classification of Headache Disorders created similar difficulties by abandoning the term symptomatic TN for manifestations caused by major neurologic disease, such as tumors or multiple sclerosis. These diagnostic challenges hinder the triage of TN patients for therapy and clinical trials, and hamper the design of treatment guidelines. In response to these shortcomings, we have developed a classification of TN that aligns with the nosology of other neurologic disorders and neuropathic pain. We propose 3 diagnostic categories. Classical TN requires demonstration of morphologic changes in the trigeminal nerve root from vascular compression. Secondary TN is due to an identifiable underlying neurologic disease. TN of unknown etiology is labeled idiopathic. Diagnostic certainty is graded possible when pain paroxysms occur in the distribution of the trigeminal nerve branches. Triggered paroxysms permit the designation of clinically established TN and probable neuropathic pain. Imaging and neurophysiologic tests that establish the etiology of classical or secondary TN determine definite neuropathic pain

Modernizing persistence–bioaccumulation–toxicity (PBT) assessment with high throughput animal-free methods

The assessment of persistence (P), bioaccumulation (B), and toxicity (T) of a chemical is a crucial first step at ensuring chemical safety and is a cornerstone of the European Union’s chemicals regulation REACH (Registration, Evaluation, Authorization, and Restriction of Chemicals). Existing methods for PBT assessment are overly complex and cumbersome, have produced incorrect conclusions, and rely heavily on animal-intensive testing. We explore how new-approach methodologies (NAMs) can overcome the limitations of current PBT assessment. We propose two innovative hazard indicators, termed cumulative toxicity equivalents (CTE) and persistent toxicity equivalents (PTE). Together they are intended to replace existing PBT indicators and can also accommodate the emerging concept of PMT (where M stands for mobility). The proposed “toxicity equivalents” can be measured with high throughput in vitro bioassays. CTE refers to the toxic effects measured directly in any given sample, including single chemicals, substitution products, or mixtures. PTE is the equivalent measure of cumulative toxicity equivalents measured after simulated environmental degradation of the sample. With an appropriate panel of animal-free or alternative in vitro bioassays, CTE and PTE comprise key environmental and human health hazard indicators. CTE and PTE do not require analytical identification of transformation products and mixture components but instead prompt two key questions: is the chemical or mixture toxic, and is this toxicity persistent or can it be attenuated by environmental degradation? Taken together, the proposed hazard indicators CTE and PTE have the potential to integrate P, B/M and T assessment into one high-throughput experimental workflow that sidesteps the need for analytical measurements and will support the Chemicals Strategy for Sustainability of the European Union

Modernizing persistence–bioaccumulation–toxicity (PBT) assessment with high throughput animal-free methods

The assessment of persistence (P), bioaccumulation (B), and toxicity (T) of a chemical is a crucial first step at ensuring chemical safety and is a cornerstone of the European Union’s chemicals regulation REACH (Registration, Evaluation, Authorization, and Restriction of Chemicals). Existing methods for PBT assessment are overly complex and cumbersome, have produced incorrect conclusions, and rely heavily on animal-intensive testing. We explore how new-approach methodologies (NAMs) can overcome the limitations of current PBT assessment. We propose two innovative hazard indicators, termed cumulative toxicity equivalents (CTE) and persistent toxicity equivalents (PTE). Together they are intended to replace existing PBT indicators and can also accommodate the emerging concept of PMT (where M stands for mobility). The proposed “toxicity equivalents” can be measured with high throughput in vitro bioassays. CTE refers to the toxic effects measured directly in any given sample, including single chemicals, substitution products, or mixtures. PTE is the equivalent measure of cumulative toxicity equivalents measured after simulated environmental degradation of the sample. With an appropriate panel of animal-free or alternative in vitro bioassays, CTE and PTE comprise key environmental and human health hazard indicators. CTE and PTE do not require analytical identification of transformation products and mixture components but instead prompt two key questions: is the chemical or mixture toxic, and is this toxicity persistent or can it be attenuated by environmental degradation? Taken together, the proposed hazard indicators CTE and PTE have the potential to integrate P, B/M and T assessment into one high-throughput experimental workflow that sidesteps the need for analytical measurements and will support the Chemicals Strategy for Sustainability of the European Union.ISSN:0340-5761ISSN:1432-073

Разработка автоматизированной системы блока эжектора установки комплексной подготовки газа

Описание технологического процесса. Выбор структуры АСУ. Подбор датчиков, контроллерного оборудования, исполнительных устройств. Раработка алгоритмов управления для блока подготовки газа УКПГDescription of the technological process. Selection of the structure of automatic control system. Selection of sensors, control equipment, executive devices. Development of control algorithms for gas preparation unit of installation of complex gas preparation

Oncogenic ERBB3 Mutations in Human Cancers

SummaryThe human epidermal growth factor receptor (HER) family of tyrosine kinases is deregulated in multiple cancers either through amplification, overexpression, or mutation. ERBB3/HER3, the only member with an impaired kinase domain, although amplified or overexpressed in some cancers, has not been reported to carry oncogenic mutations. Here, we report the identification of ERBB3 somatic mutations in ∼11% of colon and gastric cancers. We found that the ERBB3 mutants transformed colonic and breast epithelial cells in a ligand-independent manner. However, the mutant ERBB3 oncogenic activity was dependent on kinase-active ERBB2. Furthermore, we found that anti-ERBB antibodies and small molecule inhibitors effectively blocked mutant ERBB3-mediated oncogenic signaling and disease progression in vivo

Separation Control on a High-Lift Airfoil using Vortex Generator Jets at High Reynolds numbers

This work focuses on an active flow control system for a 2D two element high-lift airfoil at high Reynolds numbers up to Re= 9.2 · 106 and a Mach number of Ma= 0.15. Additional test cases at different Reynolds-and Mach numbers up to Re=12.21 · 106 at Ma=0.2 complete these measurements. The experiments were done in the cryogenic test facility DNW-KKK. The model is equipped with vortex generator jets close to the leading edge on the pressure side to suppress a turbulent leading edge stall. The experiments clearly show that the system can prevent stall but the gain of lift is reduced at high Reynolds numbers. The additional lift primarily depends on the flow rate. The influence of the actuation frequency is not clear but higher frequencies seem to be more efficient. In most cases dynamic blowing exceeds static blowing. A variation of the Mach number with constant Reynolds number and AFC parameters results in a constant increase of lift whereas the additional angle of attack becomes higher

Active Control of Leading-Edge Separation within the German Flow Control Network

The paper describes experiments with a 2D two-element high-lift airfoil with active flow control in a 2.8m windtunnel. The flow control system is integrated into the nose region of the airfoil to delay the onset of leading-edge stall, it consists of pulsed vortex generator jets that utilize compressed air. The results indicate that active flow control can be applied at a practical high-lift system. The pulsed vortex generator jets effectively delay the onset of separation at the main element and increase amax and cl,max respectively. However, the margin that can be gained is very dependent on the overall stall behavior of the airfoil

Active Control of Leading Edge Flow Separation for a Swept High-Lift Airfoil

This paper presents an active flow control swept wing experiment. The wind tunnel measurements were conducted with a two-element airfoil in high-lift configuration at Reynolds numbers of 1.9M and 2.5M and a corresponding Mach number of 0.14 and 0.18. Previous 2D wind tunnel experiments revealed a significant benefit of the AFC system. Based on this results an investigation with a swept wing (Λ=30°) was carried out to determinate the influence of a 3D boundary layer to the AFC system. The investigation was performed in the low speed wind tunnel DNW-NWB1 at Braunschweig, Germany. The AFC system was located close to the attachment line on the pressure side and consists of co-rotation vortex generator jets to suppress the leading edge stall at the airfoil. The jets can be run either in “static” mode or as dynamically pulsed jets. The AFC system used solenoid fast switch vales with can run with reasonable high frequencies up to F+=12. The measurements allow to determinate the effects of frequency and momentum coefficient on the swept wing. The results show that the AFC system can increase the maximum lift. It seems to be that the actuation frequency and momentum coefficient have a significant influence to the performance of the system. For all cases dynamic blowing is noticeably more effective than constant blowing

Influence of the actuation waveform on the performance of piezoelectric stick-slip actuators

Performance and efficiency of piezo-electric stick-slip actuators are dependent on the waveform of the electrical actuation of the piezo-stack. This paper compares between a conventional saw-tooth actuation with two waveforms that feature softer acceleration in order to minimize the duration of the slip-phase. It is shown that the proposed waveforms increase both maximum mechanical output power (by 43%) and overall efficiency (by 25%) of the examined actuator

Modular Test Bed for Performance Assessment of Piezoelectric Stick-Slip Actuators

Stepping piezoelectric actuators based on the stick-slip effect inherently make use of a friction contact between stator and rotor. This contact defines not only the actuator’s performance but also is prone to wear and tear. For broad use, the actuator has to be able to perform around 1 million strokes. To assess the actuator’s performance in terms of force, speed, mechanical output, electrical input, and long-term stability under different load- and environmental conditions, as well as different friction partners, a dedicated test bed for a LSPA30µXS motor by C-TEC has to be set up. The assessed actuator is the smallest of C-TEC’s LSPA-series. It consists of a piezo stack (2.5 x 2.5 x 5mm³) mounted in a diamond-shaped lever structure (8.6 x 3.9 x 5 mm³) to enlarge its stroke. This is then applied to a rectangular rod of 12 mm length. On this rod a clamp is mounted with a defined pre-load that is able to slide given a certain relative acceleration that determines the step size and the direction of movement. This is achieved by applying a dedicated signal of 100 V amplitude to the stack. The test bed consists of several modules for measurement and counter-force creation based on the requirements of three test modi. Mode S lets the actuator run against a linear spring thus leading to quick measurement of blocking force and no-load velocity. Mode F provides a constant force to derive single points in the actuator’s characteristic curve. Finally, mode D derives the actuator’s durability by letting the actuator perform a certain force/velocity profile. For each mode, a counter-force module is provided. For mode S a set of springs of different stiffness is used. For mode F a weight-lifting module is introduced also leading to constant forces in one direction. The D-mode is accomplished by a voice-coil actuator that is programmed in a way to provide arbitrary force-velocity curves. The test bed is controlled by a dedicated LabView program running on a standard PC. The PC also collects data provided by the different sensors. Using a Keyence, Osaka, JP laser triangulator (type LK-H052), the actual position of the clamp can be determined. Using a two-channel laser vibrometer by Polytec, Waldbronn, DE (type OVF-2502) provides phase-sensitive information of the piezo stack as well as the movement of the rod. The LabView software uses a Type NI PCI-7830R measurement card to collect data of the laser triangulator, the force sensor on the mechanical side and voltage and current applied to the actuator on the electrical side. Thus the efficiency of the actuator can be derived. Especially in mode D arbitrary load curves can be defined and both directions of movement can be assessed. Thus, a function generator is also included in the software. The whole test stand can be placed under an acrylic glass hood allowing the application of temperatures between 5 and 60°C and relative humidity between 50 and 100%. The described test stand has been set up to assess the actuator’s performance under different conditions of load, environment and internal friction parameters. Also, the influence of different friction partners on performance and lifetime can be assessed. The modular concept allows quick assessment of stall force and no-load speed (mode S), the assessment of the complete characteristic curve (mode F) and lifetime-tests under defined conditions (mode D). Using the described test stand, the energy efficiency of the LSPA30µXS actuator will be optimized in the future