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NMR standardization approach that uses the 2H integral of deuterated solvent for quantitative multinuclear analysis of pharmaceuticals is described. As a proof of principle, the existing NMR procedure for the analysis of heparin products according to US Pharmacopeia monograph is extended to the determination of Na+ and Cl- content in this matrix. Quantification is performed based on the ratio of a 23Na (35Cl) NMR integral and 2H NMR signal of deuterated solvent, D2O, acquired using the specific spectrometer hardware. As an alternative, the possibility of 133Cs standardization using the addition of Cs2CO3 stock solution is shown. Validation characteristics (linearity, repeatability, sensitivity) are evaluated. A holistic NMR profiling of heparin products can now also be used for the quantitative determination of inorganic compounds in a single analytical run using a single sample. In general, the new standardization methodology provides an appealing alternative for the NMR screening of inorganic and organic components in pharmaceutical products.
Nuclear magnetic resonance (NMR) spectrometric methods for the quantitative analysis of pure heparin in crude heparin is proposed. For quantification, a two-step routine was developed using a USP heparin reference sample for calibration and benzoic acid as an internal standard. The method was successfully validated for its accuracy, reproducibility, and precision. The methodology was used to analyze 20 authentic porcine heparinoid samples having heparin content between 4.25 w/w % and 64.4 w/w %. The characterization of crude heparin products was further extended to a simultaneous analysis of these common ions: sodium, calcium, acetate and chloride. A significant, linear dependence was found between anticoagulant activity and assayed heparin content for thirteen heparinoids samples, for which reference data were available. A Diffused-ordered NMR experiment (DOSY) can be used for qualitative analysis of specific glycosaminoglycans (GAGs) in heparinoid matrices and, potentially, for quantitative prediction of molecular weight of GAGs. NMR spectrometry therefore represents a unique analytical method suitable for the simultaneous quantitative control of organic and inorganic composition of crude heparin samples (especially heparin content) as well as an estimation of other physical and quality parameters (molecular weight, animal origin and activity).
Damage of reinforced concrete (RC) frames with masonry infill walls has been observed after many earthquakes. Brittle behaviour of the masonry infills in combination with the ductile behaviour of the RC frames makes infill walls prone to damage during earthquakes. Interstory deformations lead to an interaction between the infill and the RC frame, which affects the structural response. The result of this interaction is significant damage to the infill wall and sometimes to the surrounding structural system too. In most design codes, infill walls are considered as non-structural elements and neglected in the design process, because taking into account the infills and considering the interaction between frame and infill in software packages can be complicated and impractical. A good way to avoid negative aspects arising from this behavior is to ensure no or low-interaction of the frame and infill wall, for instance by decoupling the infill from the frame. This paper presents the numerical study performed to investigate new connection system called INODIS (Innovative Decoupled Infill System) for decoupling infill walls from surrounding frame with the aim to postpone infill activation to high interstory drifts thus reducing infill/frame interaction and minimizing damage to both infills and frames. The experimental results are first used for calibration and validation of the numerical model, which is then employed for investigating the influence of the material parameters as well as infill’s and frame’s geometry on the in-plane behaviour of the infilled frames with the INODIS system. For all the investigated situations, simulation results show significant improvements in behaviour for decoupled infilled RC frames in comparison to the traditionally infilled frames.
In proton therapy, the dose from secondary neutrons to the patient can contribute to side effects and the creation of secondary cancer. A simple and fast detection system to distinguish between dose from protons and neutrons both in pretreatment verification as well as potentially in vivo monitoring is needed to minimize dose from secondary neutrons. Two 3 mm long, 1 mm diameter organic scintillators were tested for candidacy to be used in a proton–neutron discrimination detector. The SCSF-3HF (1500) scintillating fibre (Kuraray Co. Chiyoda-ku, Tokyo, Japan) and EJ-260 plastic scintillator (Eljen Technology, Sweetwater, TX, USA) were irradiated at the TRIUMF Neutron Facility and the Proton Therapy Research Centre. In the proton beam, we compared the raw Bragg peak and spread-out Bragg peak response to the industry standard Markus chamber detector. Both scintillator sensors exhibited quenching at high LET in the Bragg peak, presenting a peak-to-entrance ratio of 2.59 for the EJ-260 and 2.63 for the SCSF-3HF fibre, compared to 3.70 for the Markus chamber. The SCSF-3HF sensor demonstrated 1.3 times the sensitivity to protons and 3 times the sensitivity to neutrons as compared to the EJ-260 sensor. Combined with our equations relating neutron and proton contributions to dose during proton irradiations, and the application of Birks’ quenching correction, these fibres provide valid candidates for inexpensive and replicable proton-neutron discrimination detectors
Landslides, rock falls or related subaerial and subaqueous mass slides can generate devastating impulse waves in adjacent waterbodies. Such waves can occur in lakes and fjords, or due to glacier calving in bays or at steep ocean coastlines. Infrastructure and residential houses along coastlines of those waterbodies are often situated on low elevation terrain, and are potentially at risk from inundation. Impulse waves, running up a uniform slope and generating an overland flow over an initially dry adjacent horizontal plane, represent a frequently found scenario, which needs to be better understood for disaster planning and mitigation. This study presents a novel set of large-scale flume test focusing on solitary waves propagating over a 1:14.5 slope and breaking onto a horizontal section. Examining the characteristics of overland flow, this study gives, for the first time, insight into the fundamental process of overland flow of a broken solitary wave: its shape and celerity, as well as its momentum when wave breaking has taken place beforehand.
In this study, the performance of an integrated body-imaging array for 7 T with 32 radiofrequency (RF) channels under consideration of local specific absorption rate (SAR), tissue temperature, and thermal dose limits was evaluated and the imaging performance was compared with a clinical 3 T body coil.
Thirty-two transmit elements were placed in three rings between the bore liner and RF shield of the gradient coil. Slice-selective RF pulse optimizations for B1 shimming and spokes were performed for differently oriented slices in the body under consideration of realistic constraints for power and local SAR. To improve the B1+ homogeneity, safety assessments based on temperature and thermal dose were performed to possibly allow for higher input power for the pulse optimization than permissible with SAR limits.
The results showed that using two spokes, the 7 T array outperformed the 3 T birdcage in all the considered regions of interest. However, a significantly higher SAR or lower duty cycle at 7 T is necessary in some cases to achieve similar B1+ homogeneity as at 3 T. The homogeneity in up to 50 cm-long coronal slices can particularly benefit from the high RF shim performance provided by the 32 RF channels. The thermal dose approach increases the allowable input power and the corresponding local SAR, in one example up to 100 W/kg, without limiting the exposure time necessary for an MR examination.
In conclusion, the integrated antenna array at 7 T enables a clinical workflow for body imaging and comparable imaging performance to a conventional 3 T clinical body coil.
The subtilase family (S8), a member of the clan SB of serine proteases are ubiquitous in all kingdoms of life and fulfil different physiological functions. Subtilases are divided in several groups and especially subtilisins are of interest as they are used in various industrial sectors. Therefore, we searched for new subtilisin sequences of the family Bacillaceae using a data mining approach. The obtained 1,400 sequences were phylogenetically classified in the context of the subtilase family. This required an updated comprehensive overview of the different groups within this family. To fill this gap, we conducted a phylogenetic survey of the S8 family with characterised holotypes derived from the MEROPS database. The analysis revealed the presence of eight previously uncharacterised groups and 13 subgroups within the S8 family. The sequences that emerged from the data mining with the set filter parameters were mainly assigned to the subtilisin subgroups of true subtilisins, high-alkaline subtilisins, and phylogenetically intermediate subtilisins and represent an excellent source for new subtilisin candidates.
In general aviation, too, it is desirable to be able to operate existing internal combustion engines with fuels that produce less CO₂ than Avgas 100LL being widely used today It can be assumed that, in comparison, the fuels CNG, LPG or LNG, which are gaseous under normal conditions, produce significantly lower emissions. Necessary propulsion system adaptations were investigated as part of a research project at Aachen University of Applied Sciences.
Biomedical applications of magnetic nanoparticles (MNP) fundamentally rely on the particles’ magnetic relaxation as a response to an alternating magnetic field. The magnetic relaxation complexly depends on the interplay of MNP magnetic and physical properties with the applied field parameters. It is commonly accepted that particle core size is a major contributor to signal generation in all the above applications, however, most MNP samples comprise broad distribution spanning nm and more. Therefore, precise knowledge of the exact contribution of individual core sizes to signal generation is desired for optimal MNP design generally for each application. Specifically, we present a magnetic relaxation simulation-driven analysis of experimental frequency mixing magnetic detection (FMMD) for biosensing to quantify the contributions of individual core size fractions towards signal generation. Applying our method to two different experimental MNP systems, we found the most dominant contributions from approx. 20 nm sized particles in the two independent MNP systems. Additional comparison between freely suspended and immobilized MNP also reveals insight in the MNP microstructure, allowing to use FMMD for MNP characterization, as well as to further fine-tune its applicability in biosensing.
Automated driving is now possible in diverse road and traffic conditions. However, there are still situations that automated vehicles cannot handle safely and efficiently. In this case, a Transition of Control (ToC) is necessary so that the driver takes control of the driving. Executing a ToC requires the driver to get full situation awareness of the driving environment. If the driver fails to get back the control in a limited time, a Minimum Risk Maneuver (MRM) is executed to bring the vehicle into a safe state (e.g., decelerating to full stop). The execution of ToCs requires some time and can cause traffic disruption and safety risks that increase if several vehicles execute ToCs/MRMs at similar times and in the same area. This study proposes to use novel C-ITS traffic management measures where the infrastructure exploits V2X communications to assist Connected and Automated Vehicles (CAVs) in the execution of ToCs. The infrastructure can suggest a spatial distribution of ToCs, and inform vehicles of the locations where they could execute a safe stop in case of MRM. This paper reports the first field operational tests that validate the feasibility and quantify the benefits of the proposed infrastructure-assisted ToC and MRM management. The paper also presents the CAV and roadside infrastructure prototypes implemented and used in the trials. The conducted field trials demonstrate that infrastructure-assisted traffic management solutions can reduce safety risks and traffic disruptions.