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Conventional EEG devices cannot be used in everyday life and hence, past decade research has been focused on Ear-EEG for mobile, at-home monitoring for various applications ranging from emotion detection to sleep monitoring. As the area available for electrode contact in the ear is limited, the electrode size and location play a vital role for an Ear-EEG system. In this investigation, we present a quantitative study of ear-electrodes with two electrode sizes at different locations in a wet and dry configuration. Electrode impedance scales inversely with size and ranges from 450 kΩ to 1.29 MΩ for dry and from 22 kΩ to 42 kΩ for wet contact at 10 Hz. For any size, the location in the ear canal with the lowest impedance is ELE (Left Ear Superior), presumably due to increased contact pressure caused by the outer-ear anatomy. The results can be used to optimize signal pickup and SNR for specific applications. We demonstrate this by recording sleep spindles during sleep onset with high quality (5.27 μVrms).
Wearable EEG has gained popularity in recent years driven by promising uses outside of clinics and research. The ubiquitous application of continuous EEG requires unobtrusive form-factors that are easily acceptable by the end-users. In this progression, wearable EEG systems have been moving from full scalp to forehead and recently to the ear. The aim of this study is to demonstrate that emerging ear-EEG provides similar impedance and signal properties as established forehead EEG. EEG data using eyes-open and closed alpha paradigm were acquired from ten healthy subjects using generic earpieces fitted with three custom-made electrodes and a forehead electrode (at Fpx) after impedance analysis. Inter-subject variability in in-ear electrode impedance ranged from 20 kΩ to 25 kΩ at 10 Hz. Signal quality was comparable with an SNR of 6 for in-ear and 8 for forehead electrodes. Alpha attenuation was significant during the eyes-open condition in all in-ear electrodes, and it followed the structure of power spectral density plots of forehead electrodes, with the Pearson correlation coefficient of 0.92 between in-ear locations ELE (Left Ear Superior) and ERE (Right Ear Superior) and forehead locations, Fp1 and Fp2, respectively. The results indicate that in-ear EEG is an unobtrusive alternative in terms of impedance, signal properties and information content to established forehead EEG.
Introduction: In peripheral percutaneous (VA) extracorporeal membrane oxygenation (ECMO) procedures the femoral arteries perfusion route has inherent disadvantages regarding poor upper body perfusion due to watershed. With the advent of new long flexible cannulas an advancement of the tip up to the ascending aorta has become feasible. To investigate the impact of such long endoluminal cannulas on upper body perfusion, a Computational Fluid Dynamics (CFD) study was performed considering different support levels and three cannula positions.
Methods: An idealized literature-based- and a real patient proximal aortic geometry including an endoluminal cannula were constructed. The blood flow was considered continuous. Oxygen saturation was set to 80% for the blood coming from the heart and to 100% for the blood leaving the cannula. 50% and 90% venoarterial support levels from the total blood flow rate of 6 l/min were investigated for three different positions of the cannula in the aortic arch.
Results: For both geometries, the placement of the cannula in the ascending aorta led to a superior oxygenation of all aortic blood vessels except for the left coronary artery. Cannula placements at the aortic arch and descending aorta could support supra-aortic arteries, but not the coronary arteries. All positions were able to support all branches with saturated blood at 90% flow volume.
Conclusions: In accordance with clinical observations CFD analysis reveals, that retrograde advancement of a long endoluminal cannula can considerably improve the oxygenation of the upper body and lead to oxygen saturation distributions similar to those of a central cannulation.
In this paper, we will provide a feasible mission design for a multiple-rendezvous mission to Jupiter's Trojans. It is based on solar electric propulsion, as being currently used on the DAWN spacecraft, and other flight-proven technology. First, we have selected a set of mission objectives, the prime objective being the detection of water -especially subsurface water -to provide evidence for the Trojans' formation at large solar distances. Based on DAWN and other comparable missions, we have determined suitable payload instruments to achieve these objectives. Afterwards, we have designed a spacecraft that is able to carry the selected payload to the Trojan region and rendezvous successively with three target bodies within a maximum mission duration of 15 years. Accurate low-thrust trajectories have been obtained with a global low-thrust trajectory optimization program (InTrance). During the transfer from Earth to the first target, the spacecraft is propelled by two RIT-22 ion engines from EADS Astrium, whereas a single RIT-15 is used for transfers within the Trojan region to reduce the required power. For power generation, the spacecraft uses a multi-junction solar array that is supported by concentrators. To achieve moderate mission costs, we have restricted the launch mass to a maximum of 1600 kg, the maximum interplanetary injection capability of a Soyuz/Fregat launcher. Our final layout has a mass of 1400 kg, yielding a margin of about 14%. Nestor (a member of the L4-population) was determined as the first mission target. It can be reached within 4.6 years from launch. The fuel mass ratio for this transfer is about 35%. The stay time at Nestor is 1.2 years. Eurymedon was selected as the second target (transfer time 3.5 years, stay time 3.0 years) and Irus as the third target (transfer time 2.2 years). The transfers within the Trojan L4-population can be accomplished with fuel mass ratios of about 3% for each trajectory leg. Including the stay times in orbit around the targets, the mission can be accomplished within a total duration of about 14.5 years. According to our mission analysis, it is also feasible to fly to the L5-population with similar flight times. It has to be noted that -for a first analysis -we have taken only the named targets into account. Allowing also rendezvous with unnamed objects will very likely decrease the mission duration. Based on a scaling of DAWN's mission costs (due to comparable scientific instruments and mission objectives), and taking into account the longer mission duration and the potential re-use of already developed technology, we have estimated that these three rendezvous can be accomplished with a budget of about 250 Million Euros, i.e. about 25% of ROSETTA's budget.
Technical assessment of Brayton cycle heat pumps for the integration in hybrid PV-CSP power plants
(2022)
The hybridization of Concentrated Solar Power (CSP) and Photovoltaics (PV) systems is a promising approach to reduce costs of solar power plants, while increasing dispatchability and flexibility of power generation. High temperature heat pumps (HT HP) can be utilized to boost the salt temperature in the thermal energy storage (TES) of a Parabolic Trough Collector (PTC) system from 385 °C up to 565 °C. A PV field can supply the power for the HT HP, thus effectively storing the PV power as thermal energy. Besides cost-efficiently storing energy from the PV field, the power block efficiency of the overall system is improved due to the higher steam parameters. This paper presents a technical assessment of Brayton cycle heat pumps to be integrated in hybrid PV-CSP power plants. As a first step, a theoretical analysis was carried out to find the most suitable working fluid. The analysis included the fluids Air, Argon (Ar), Nitrogen (N2) and Carbon dioxide (CO2). N2 has been chosen as the optimal working fluid for the system. After the selection of the ideal working medium, different concepts for the arrangement of a HT HP in a PV-CSP hybrid power plant were developed and simulated in EBSILON®Professional. The concepts were evaluated technically by comparing the number of components required, pressure losses and coefficient of performance (COP).
The role of Germany, Japan and the United States on the ECU-bond markets / Hans Wilhelm Mackenstein
(1991)
Books Reviewed - European Democratization since 1800 edited by J. Garrard, V. Tolz and R. White
(2000)
A technology reference study for a solar polar mission is presented. The study uses novel analytical methods to quantify the mission design space including the required sail performance to achieve a given solar polar observation angle within a given timeframe and thus to derive mass allocations for the remaining spacecraft sub-systems, that is excluding the solar sail sub-system. A parametric, bottom-up, system mass budget analysis is then used to establish the required sail technology to deliver a range of science payloads, and to establish where such payloads can be delivered to within a given timeframe. It is found that a solar polar mission requires a solar sail of side-length 100–125 m to deliver a ‘sufficient value’ minimum science payload, and that a 2.5 μm sail film substrate is typically required, however the design is much less sensitive to the boom specific mass.
Purpose
To demonstrate that high quality T₂-weighted (T2w) turbo spin-echo (TSE) imaging of the complete prostate can be achieved routinely and within safety limits at 7 T, using an external transceive body array coil only.
Methods
Nine healthy volunteers and 12 prostate cancer patients were scanned on a 7 T whole-body system. Preparation consisted of B₀ and radiofrequency shimming and localized flip angle calibration. T₁ and T₂ relaxation times were measured and used to define the T2w-TSE protocol. T2w imaging was performed using a TSE sequence (pulse repetition time/echo time 3000–3640/71 ms) with prolonged excitation and refocusing pulses to reduce specific absorption rate.
Results
High quality T2w TSE imaging was performed in less than 2 min in all subjects. Tumors of patients with gold-standard tumor localization (MR-guided biopsy or prostatectomy) were well visualized on 7 T imaging (n = 3). The number of consecutive slices achievable within a 10-g averaged specific absorption rate limit of 10 W/kg was ≥28 in all subjects, sufficient for full prostate coverage with 3-mm slices in at least one direction.
Conclusion
High quality T2w TSE prostate imaging can be performed routinely and within specific absorption rate limits at 7 T with an external transceive body array.
It is well known that the already large dielectric constants of some electrolytes like BaTiO₃ can be enhanced further by adding metallic (e.g. Ni, Cu or Ag) nanoparticles. The enhancement can be quite large, a factor of more than 1000 is possible. The consequences for the properties will be discussed in the present paper applying a brick-layer model (BLM) for calculating dc-resistivities of thin layers and a modified one (PBLM) that includes percolation for calculating dielectric properties of these materials. The PBLM results in an at least qualitative description and understanding of the physical phenomena: This model gives an explanation for the steep increase of the dielectric constant below the percolation threshold and why this increase is connected to a dramatic decrease of the breakdown voltage as well as the ability of storing electrical energy. We conclude that metallic electrolyte composites like BaTiO₃ are not appropriate for energy storage.
The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are closely related nuclear receptors involved in drug metabolism and play important roles in the mechanism of phenobarbital (PB)-induced rodent nongenotoxic hepatocarcinogenesis. Here, we have used a humanized CAR/PXR mouse model to examine potential species differences in receptor-dependent mechanisms underlying liver tissue molecular responses to PB. Early and late transcriptomic responses to sustained PB exposure were investigated in liver tissue from double knock-out CAR and PXR (CARᴷᴼ-PXRᴷᴼ), double humanized CAR and PXR (CARʰ-PXRʰ), and wild-type C57BL/6 mice. Wild-type and CARʰ-PXRʰ mouse livers exhibited temporally and quantitatively similar transcriptional responses during 91 days of PB exposure including the sustained induction of the xenobiotic response gene Cyp2b10, the Wnt signaling inhibitor Wisp1, and noncoding RNA biomarkers from the Dlk1-Dio3 locus. Transient induction of DNA replication (Hells, Mcm6, and Esco2) and mitotic genes (Ccnb2, Cdc20, and Cdk1) and the proliferation-related nuclear antigen Mki67 were observed with peak expression occurring between 1 and 7 days PB exposure. All these transcriptional responses were absent in CARᴷᴼ-PXRᴷᴼ mouse livers and largely reversible in wild-type and CARʰ-PXRʰ mouse livers following 91 days of PB exposure and a subsequent 4-week recovery period. Furthermore, PB-mediated upregulation of the noncoding RNA Meg3, which has recently been associated with cellular pluripotency, exhibited a similar dose response and perivenous hepatocyte-specific localization in both wild-type and CARʰ-PXRʰ mice. Thus, mouse livers coexpressing human CAR and PXR support both the xenobiotic metabolizing and the proliferative transcriptional responses following exposure to PB.
Manufacturing companies across multiple industries face an increasingly dynamic and unpredictable environment. This development can be seen on both the market and supply side. To respond to these challenges, manufacturing companies must implement smart manufacturing systems and become more flexible and agile. The flexibility in operational planning regarding the scheduling and sequencing of customer orders needs to be increased and new structures must be implemented in manufacturing systems’ fundamental design as they constitute much of the operational flexibility available. To this end, smart and more flexible solutions for production planning and control (PPC) are developed. However, scheduling or sequencing is often only considered isolated in a predefined stable environment. Moreover, their orientation on the fundamental logic of the existing IT solutions and their applicability in a dynamic environment is limited. This paper presents a conceptual model for a task-based description logic that can be applied to factory planning, technology planning, and operational control. By using service-oriented architectures, the goal is to generate smart manufacturing systems. The logic is designed to allow for easy and automated maintenance. It is compatible with the existing resource and process allocation logic across operational and strategic factory and production planning.
There is a growing demand for more flexibility in manufacturing to counter the volatility and unpredictability of the markets and provide more individualization for customers. However, the design and implementation of flexibility within manufacturing systems are costly and only economically viable if applicable to actual demand fluctuations. To this end, companies are considering additive manufacturing (AM) to make production more flexible. This paper develops a conceptual model for the impact quantification of AM on volume and mix flexibility within production systems in the early stages of the factory-planning process. Together with the model, an application guideline is presented to help planners with the flexibility quantification and the factory design process. Following the development of the model and guideline, a case study is presented to indicate the potential impact additive technologies can have on manufacturing flexibility Within the case study, various scenarios with different production system configurations and production programs are analyzed, and the impact of the additive technologies on volume and mix flexibility is calculated. This work will allow factory planners to determine the potential impacts of AM on manufacturing flexibility in an early planning stage and design their production systems accordingly.
This paper describes the procedure on the evaluation of the masonry chapter for the next generation of Eurocode 8, the European Standard for earthquake-resistant design. In CEN, TC 250/SC8, working group WG 1 has been established to support the subcommittee on the topic of masonry on both design of new structures (EN1998-1) and assessment of existing structures (EN1998-3). The aim is to elaborate suggestions for amendments which fit the current state of the art in masonry and earthquake-resistant design. Focus will be on modelling, simplified methods, linear-analysis (q-values, overstrength-values), nonlinear procedures, out-of-plane design as well as on clearer definition of limit states. Beside these, topics related to general material properties, reinforced masonry, confined masonry, mixed structures and non-structural infills will be covered too. This paper presents the preliminary work and results up to the submission date.
Water suppliers are faced with the great challenge of achieving high-quality and, at the same time, low-cost water supply. In practice, the focus is set on the most beneficial maintenance measures and/or capacity adaptations of existing water distribution systems (WDS). Since climatic and demographic influences will pose further challenges in the future, the resilience enhancement of WDS, i.e. the enhancement of their capability to withstand and recover from disturbances, has been in particular focus recently. To assess the resilience of WDS, metrics based on graph theory have been proposed. In this study, a promising approach is applied to assess the resilience of the WDS for a district in a major German City. The conducted analysis provides insight into the process of actively influencing the
resilience of WDS
Water suppliers are faced with the great challenge of achieving high-quality and, at the same time, low-cost water supply. Since climatic and demographic influences will pose further challenges in the future, the resilience enhancement of water distribution systems (WDS), i.e. the enhancement of their capability to withstand and recover from disturbances, has been in particular focus recently. To assess the resilience of WDS, graph-theoretical metrics have been proposed. In this study, a promising approach is first physically derived analytically and then applied to assess the resilience of the WDS for a district in a major German City. The topology based resilience index computed for every consumer node takes into consideration the resistance of the best supply path as well as alternative supply paths. This resistance of a supply path is derived to be the dimensionless pressure loss in the pipes making up the path. The conducted analysis of a present WDS provides insight into the process of actively influencing the resilience of WDS locally and globally by adding pipes. The study shows that especially pipes added close to the reservoirs and main branching points in the WDS result in a high resilience enhancement of the overall WDS.
Water distribution systems are an essential supply infrastructure for cities. Given that climatic and demographic influences will pose further challenges for these infrastructures in the future, the resilience of water supply systems, i.e. their ability to withstand and recover from disruptions, has recently become a subject of research. To assess the resilience of a WDS, different graph-theoretical approaches exist. Next to general metrics characterizing the network topology, also hydraulic and technical restrictions have to be taken into account. In this work, the resilience of an exemplary water distribution network of a major German city is assessed, and a Mixed-Integer Program is presented which allows to assess the impact of capacity adaptations on its resilience.
The Volatility Framework is a collection of tools for the analysis of computer RAM. The framework offers a multitude of analysis options and is used by many investigators worldwide. Volatility currently comes with a command line interface only, which might be a hinderer for some investigators to use the tool. In this paper we present a GUI and extensions for the Volatility Framework, which on the one hand simplify the usage of the tool and on the other hand offer additional functionality like storage of results in a database, shortcuts for long Volatility Framework command sequences, and entirely new commands based on correlation of data stored in the database.
By DLR-contact, sample return missions to the large main-belt asteroid “19, Fortuna” have been studied. The mission scenario has been based on three ion thrusters of the RIT-22 model, which is presently under space qualification, and on solar arrays equipped with triple-junction GaAs solar cells. After having designed the spacecraft, the orbit-to-orbit trajectories for both, a one-way SEP mission with a chemical sample return and an all-SEP return mission, have been optimized using a combination of artificial neural networks with evolutionary algorithms. Additionally, body-to-body trajectories have been
investigated within a launch period between 2012 and 2015. For orbit-to-orbit calculation, the launch masses of the hybrid mission and of the all-SEP mission resulted in 2.05 tons and 1.56 tons, respectively, including a scientific payload of 246 kg. For the related transfer
durations 4.14 yrs and 4.62 yrs were obtained. Finally, a comparison between the mission scenarios based on SEP and on NEP have been carried out favouring clearly SEP.
There is common agreement within the scientific community that in order to understand our local galactic environment it will be necessary to send a spacecraft into the region beyond the solar wind termination shock. Considering distances of 200 AU for a new mission, one needs a spacecraft traveling at a speed of close to 10 AU/yr in order to keep the mission duration in the range of less than 25 yrs, a transfer time postulated by European Space Agency (ESA). Two propulsion options for the mission have been proposed and discussed so far: the solar sail propulsion and the ballistic/radioisotope-electric propulsion (REP). As a further alternative, we here investigate a combination of solar-electric propulsion (SEP) and REP. The SEP stage consists of six 22-cms diameter RIT-22 ion thrusters working with a high specific impulse of 7377 s corresponding to a positive grid voltage of 5 kV. Solar power of 53 kW at begin of mission (BOM) is provided by a lightweight solar array.
Under DLR-contract, Giessen University and DLR Cologne are studying solar-electric propulsion missions (SEP) to the outer regions of the solar system. The most challenging reference mission concerns the transport of a 1.35-tons chemical lander spacecraft into an 80-RJ circular orbit around Jupiter, which would enable to place a 375 kg lander with 50 kg of scientific instruments on the surface of the icy moon "Europa". Thorough analyses show that the best solution in terms of SEP launch mass times thrusting time would be a two-stage EP module and a triple-junction solar array with concentrators which would be deployed step by step. Mission performance optimizations suggest to propel the spacecraft in the first EP stage by 6 gridded ion thrusters, running at 4.0 kV of beam voltage, which would save launch mass, and in the second stage by 4 thrusters with 1.25 to 1.5 kV of positive high voltage saving thrusting time. In this way, the launch mass of the spacecraft would be kept within 5.3 tons. Without a launcher's C3 and interplanetary gravity assists, Jupiter might be reached within about 4 yrs. The spiraling-down into the parking orbit would need another 1.8 yrs. This "large mission" can be scaled down to a smaller one, e.g., by halving all masses, the solar array power, and the number of thrusters. Due to their reliability, long lifetime and easy control, RIT-22 engines have been chosen for mission analysis. Based on precise tests, the thruster performance has been modeled.
An Interstellar – Heliopause mission using a combination of solar/radioisotope electric propulsion
(2011)
There is common agreement within the scientific community that in order to understand our local galactic environment it will be necessary to send a spacecraft into the region beyond the solar wind termination shock. Considering distances of 200 AU for a new mission, one needs a spacecraft travelling at a speed of close to 10 AU/yr in order to keep the mission duration in the range of less than 25 yrs, a transfer time postulated by ESA.Two propulsion options for the mission have been proposed and discussed so far: the solar sail propulsion and the ballistic/radioisotope electric propulsion. As a further alternative, we here investigate a combination of solar-electric propulsion and radioisotope-electric propulsion. The solar-electric propulsion stage consists of six 22 cm diameter “RIT-22”ion thrusters working with a high specific impulse of 7377 s corresponding to a positive grid voltage of 5 kV. Solar power of 53 kW BOM is provided by a light-weight solar array. The REP-stage consists of four space-proven 10 cm diameter “RIT-10” ion thrusters that will be operating one after the other for 9 yrs in total. Four advanced radioisotope generators provide 648 W at BOM. The scientific instrument package is oriented at earlier studies. For its mass and electric power requirement 35 kg and 35 W are assessed, respectively. Optimized trajectory calculations, treated in a separate contribution, are based on our “InTrance” method.The program yields a burn out of the REP stage in a distance of 79.6 AU for a usage of 154 kg of Xe propellant. With a C3 = 45,1 (km/s)2 a heliocentric probe velocity of 10 AU/yr is reached at this distance, provided a close Jupiter gravity assist adds a velocity increment of 2.7 AU/yr. A transfer time of 23.8 yrs results for this scenario requiring about 450 kg Xe for the SEP stage, jettisoned at 3 AU. We interpret the SEP/REP propulsion as a competing alternative to solar sail and ballistic/REP propulsion. Omiting a Jupiter fly-by even allows more launch flexibility, leaving the mission duration in the range of the ESA specification.
Based on the European Space Agency (ESA) Science in Space Environment (SciSpacE) community White Paper “Human Physiology – Musculoskeletal system”, this perspective highlights unmet needs and suggests new avenues for future studies in musculoskeletal research to enable crewed exploration missions. The musculoskeletal system is essential for sustaining physical function and energy metabolism, and the maintenance of health during exploration missions, and consequently mission success, will be tightly linked to musculoskeletal function. Data collection from current space missions from pre-, during-, and post-flight periods would provide important information to understand and ultimately offset musculoskeletal alterations during long-term spaceflight. In addition, understanding the kinetics of the different components of the musculoskeletal system in parallel with a detailed description of the molecular mechanisms driving these alterations appears to be the best approach to address potential musculoskeletal problems that future exploratory-mission crew will face. These research efforts should be accompanied by technical advances in molecular and phenotypic monitoring tools to provide in-flight real-time feedback.
Although several successful applications of benchtop nuclear magnetic resonance (NMR) spectroscopy in quantitative mixture analysis exist, the possibility of calibration transfer remains mostly unexplored, especially between high- and low-field NMR. This study investigates for the first time the calibration transfer of partial least squares regressions [weight average molecular weight (Mw) of lignin] between high-field (600 MHz) NMR and benchtop NMR devices (43 and 60 MHz). For the transfer, piecewise direct standardization, calibration transfer based on canonical correlation analysis, and transfer via the extreme learning machine auto-encoder method are employed. Despite the immense resolution difference between high-field and low-field NMR instruments, the results demonstrate that the calibration transfer from high- to low-field is feasible in the case of a physical property, namely, the molecular weight, achieving validation errors close to the original calibration (down to only 1.2 times higher root mean square errors). These results introduce new perspectives for applications of benchtop NMR, in which existing calibrations from expensive high-field instruments can be transferred to cheaper benchtop instruments to economize.
Time-of-flight (ToF) sensors have become an alternative to conventional distance sensing techniques like laser scanners or image based stereo. ToF sensors provide full range distance information at high frame-rates and thus have a significant impact onto current research in areas like online object recognition, collision prevention or scene reconstruction. However, ToF cameras like the photonic mixer device (PMD) still exhibit a number of challenges regarding static and dynamic effects, e.g. systematic distance errors and motion artefacts, respectively. Sensor calibration techniques reducing static system errors have been proposed and show promising results. However, current calibration techniques in general need a large set of reference data in order to determine the corresponding parameters for the calibration model. This paper introduces a new calibration approach which combines different demodulation techniques for the ToF- camera 's reference signal. Examples show, that the resulting combined demodulation technique yields improved distance values based on only two required reference data sets.
A new in vitro tool to investigate cardiac contractility under physiological mechanical conditions
(2019)
With its need for high SNR and short acquisition times, Cardiac MRI (CMR) is an intriguing target application for ultrahigh field MRI. Due to the sheer size of the upper torso, however, the known RF issues of 7T MRI are also most prominent in CMR. Recent years brought substantial progress but the full potential of the ultrahigh field for CMR is yet to be exploited. Parallel transmission (pTx) is a promising approach in this context and several groups have already reported B1 shimming for 7T CMR. In such a static pTx application amplitudes and phases of all Tx channels are adjusted individually but otherwise imaging techniques established in current clinical practice 1.5 T and 3 T are applied. More advanced forms of pTx as spatially selective excitation (SSE) using Transmit SENSE promise additional benefits like faster imaging with reduced fields of view or improved SAR control. SSE requires the full dynamic capabilities of pTx, however, and for the majority of today's implemented pTx hardware the internal synchronization of the Tx array does not easily permit external triggering as needed for CMR. Here we report a software solution to this problem and demonstrate the feasibility of CINE CMR at 7 T using a Tx array.
Handbook of space technology
(2009)
Analysis of the long-term effect of the MBST® nuclear magnetic resonance therapy on gonarthrosis
(2016)
Bioconjugates containing the GnRH-III hormone decapeptide as a targeting moiety are able to deliver chemotherapeutic agents specifically to cancer cells expressing GnRH receptors, thereby increasing their local efficacy while limiting the peripheral toxicity. However, the number of GnRH receptors on cancer cells is limited and they desensitize under continuous hormone treatment. A possible approach to increase the receptor mediated tumor targeting and consequently the cytostatic effect of the bioconjugates would be the attachment of more than one chemotherapeutic agent to one GnRH-III molecule. Here we report on the design, synthesis and biochemical characterization of multifunctional bioconjugates containing GnRH-III as a targeting moiety and daunorubicin as a chemotherapeutic agent. Two different drug design approaches were pursued. The first one was based on the bifunctional [4Lys]-GnRH-III (Glp-His-Trp-Lys-His-Asp-Trp-Lys-Pro-Gly-NH2) containing two lysine residues in positions 4 and 8, whose ϵ-amino groups were used for the coupling of daunorubicin. In the second drug design, the native GnRH-III (Glp-His-Trp-Ser-His-Asp-Trp-Lys-Pro-Gly-NH2) was used as a scaffold; an additional lysine residue was coupled to the ϵ-amino group of 8Lys in order to generate two free amino groups available for conjugation of daunorubicin. The in vitro stability/degradation of all synthesized compounds was investigated in human serum, as well as in the presence of rat liver lysosomal homogenate. Their cellular uptake was determined on human breast cancer cells and the cytostatic effect was evaluated on human breast, colon and prostate cancer cell lines. Compared with a monofunctional compound, both drug design approaches resulted in multifunctional bioconjugates with increased cytostatic effect.
Introduction
In regard of surgical training, the reproducible simulation of life-like proximal humerus fractures in human cadaveric specimens is desirable. The aim of the present study was to develop a technique that allows simulation of realistic proximal humerus fractures and to analyse the influence of rotator cuff preload on the generated lesions in regards of fracture configuration.
Materials and methods
Ten cadaveric specimens (6 left, 4 right) were fractured using a custom-made drop-test bench, in two groups. Five specimens were fractured without rotator cuff preload, while the other five were fractured with the tendons of the rotator cuff preloaded with 2 kg each. The humeral shaft and the shortened scapula were potted. The humerus was positioned at 90° of abduction and 10° of internal rotation to simulate a fall on the elevated arm. In two specimens of each group, the emergence of the fractures was documented with high-speed video imaging. Pre-fracture radiographs were taken to evaluate the deltoid-tuberosity index as a measure of bone density. Post-fracture X-rays and CT scans were performed to define the exact fracture configurations. Neer’s classification was used to analyse the fractures.
Results
In all ten cadaveric specimens life-like proximal humerus fractures were achieved. Two III-part and three IV-part fractures resulted in each group. The preloading of the rotator cuff muscles had no further influence on the fracture configuration. High-speed videos of the fracture simulation revealed identical fracture mechanisms for both groups. We observed a two-step fracture mechanism, with initial impaction of the head segment against the glenoid followed by fracturing of the head and the tuberosities and then with further impaction of the shaft against the acromion, which lead to separation of the tuberosities.
Conclusion
A high energetic axial impulse can reliably induce realistic proximal humerus fractures in cadaveric specimens. The preload of the rotator cuff muscles had no influence on initial fracture configuration. Therefore, fracture simulation in the proximal humerus is less elaborate. Using the presented technique, pre-fractured specimens are available for real-life surgical education.
The molecular events during nongenotoxic carcinogenesis and their temporal order are poorly understood but thought to include long-lasting perturbations of gene expression. Here, we have investigated the temporal sequence of molecular and pathological perturbations at early stages of phenobarbital (PB) mediated liver tumor promotion in vivo. Molecular profiling (mRNA, microRNA [miRNA], DNA methylation, and proteins) of mouse liver during 13 weeks of PB treatment revealed progressive increases in hepatic expression of long noncoding RNAs and miRNAs originating from the Dlk1-Dio3 imprinted gene cluster, a locus that has recently been associated with stem cell pluripotency in mice and various neoplasms in humans. PB induction of the Dlk1-Dio3 cluster noncoding RNA (ncRNA) Meg3 was localized to glutamine synthetase-positive hypertrophic perivenous hepatocytes, sug- gesting a role for β-catenin signaling in the dysregulation of Dlk1-Dio3 ncRNAs. The carcinogenic relevance of Dlk1-Dio3 locus ncRNA induction was further supported by in vivo genetic dependence on constitutive androstane receptor and β-catenin pathways. Our data identify Dlk1-Dio3 ncRNAs as novel candidate early biomarkers for mouse liver tumor promotion and provide new opportunities for assessing the carcinogenic potential of novel compounds.