Self-adjusting process monitoring system in series production

Modern monitoring systems in machine tools are able to detect process errors promptly. Still, the application of monitoring systems is restricted by the complexity of parameterization for save monitoring. In most cases, only specially trained personnel can handle this job especially for multi-purpose machines. The aim of the research project "Proceed" is to figure out in which extent a self-parameterization and autonomous optimization of monitoring systems in industrial series production can be realized. Therefore, a self-adjusting and self-tuning process monitoring system for series production has been developed. This system is based on multi-criteria sensor signal evaluation and is able to assess its monitoring quality quantitatively. For this purpose, the complete process chain of parameterization has been automated. For series production it is assumed, that the first process is not defective. So, process sensitive features are identified by a correlation analysis with a reference signal. The reference signal is selected through an analysis of the process state by an expert system. To assess the monitoring quality resulting from automatic parameterization, normed specific values were used. These values describe the monitoring quality with the help of the distance between a feature and its threshold normed to signal amplitude and noise. A second indicator is the reaction of the monitoring system to a synthetic error added to signal a sequence. Thus it is possible to estimate monitoring quality corresponding to automatic parameterization. The validation is carried out by a comparison between the result of the assessment and the reaction ability of the monitoring system to real process errors from milling, drilling and turning processes.DFG/DE 447/96–

Polyfunktionale Calciumphosphat-Nanopartikel als neuartige Impfstoffplattform gegen HIV-1

Synthetic nanoparticles functionalized with stabilized trimers of the HIV-1 envelope glycoprotein (Env) have become a major focus in AIDS vaccine research. The additional incorporation of T helper cell epitopes into such nanoparticles might recruit pre-existing CD4+ T cell responses induced by childhood vaccinations to provide intrastructural help (ISH) for Env-specific B cells upon immunization. In this study, calcium phosphate nanoparticles (CaPs), that encapsulate an immunodominant Tetanus Toxoid epitope (p30) and display Env trimers on the surface (T helper CaPs), were evaluated in preclinical vaccine trials. T helper CaPs induced the activation of Env-specific naïve B cells in vitro, which was not observed with soluble Env trimers. Immunization with T helper CaPs resulted in significantly stronger Env-specific humoral immune responses via ISH in mice that were immunized in advance with a licensed Tetanus vaccine. The magnitude of anti-Env antibody levels in ISH mice was comparable to a control group immunized with CpG-adjuvanted CaPs. In contrast to CpG, the induction of immune mechanisms suspected to increase the susceptibility for HIV infection was bypassed by harnessing ISH. Having provided evidence that the utilization of T helper CaPs resulted in versatile, immunomodulatory features, the nanoparticle design was improved by an orthogonal Env coupling mechanism (oCaPs). To this end, a genetically encoded aldehyde-tag (LCTPSR) was introduced at the C-terminus of native-like, soluble Env trimers. The tag-associated cysteine is post-translationally converted into a formylglycine harboring an aldehyde group, which was confirmed by mass spectrometry. This aldehyde was used for covalent bioconjugation with an aminooxy/alkyne-crosslinker. Linker-bound Env trimers (lnkr-Env) were then immobilized on the CaP surface via a Click reaction. Reporter assays based on fluorescent gel analysis and CLSM proved that the Env conjugation was highly aldehyde-specific and efficient. Most importantly, conformational ELISA and surface FACS analyses indicated that the pre-fusion conformation is preserved. oCaPs induced stronger B cell activation in vitro and higher Env-specific antibody levels in vivo than randomly coupled CaPs. Taken together, this study established a nanoparticle delivery platform for future immunomodulatory vaccine approaches and diagnostic applications in the context of various pathogens.Ein neuer Schwerpunkt der HIV Impfstoffforschung sind synthetische Nanopartikel, die mit optimierten Trimeren des Oberflächenproteins (Env) gekoppelt wurden. Der zusätzliche Einschluss von T-Helferzell-Epitopen aus humanen Impfstoffen in solche Nanopartikel macht es möglich, bestehende CD4+ T-Zellen zu rekrutieren, damit diese intrastrukturelle Hilfe (ISH) für Env-spezifische B-Zellen nach der Partikelimpfung leisten. In dieser Studie wurde die Eignung von T-Helfer-Calciumphosphat-Nanopartikeln (T-Helfer CaPs), die ein immunodominantes Tetanus-Toxoid-Epitop (p30) im Inneren und Env-Trimere auf der Oberfläche enthalten, funktionell und durch präklinische Immunisierungen untersucht. Verglichen mit löslichen Env-Trimeren konnten T-Helfer CaPs die Aktivierung Env-spezifischer, naiver B-Zellen in vitro induzieren. Immunisierungen mit T-Helfer CaPs führten zu signifikant erhöhten humoralen Immunantworten durch ISH in Mäusen, die zuvor mit einem lizensierten Tetanusimpfstoff immunisiert wurden. Die Env-Antikörperbildung in ISH-Mäusen war vergleichbar stark wie in Tieren, welche CpG-adjuvantierte CaPs erhielten. Im Gegensatz zu CpG wurden durch ISH keine Immunmechanismen induziert, die mit erhöhtem HIV-Infektionsrisiko in Verbindung gebracht werden. Infolge dieser vielversprechenden Ergebnisse wurde die Nanopartikelherstellung durch eine orthogonale Env-Kopplung optimiert (oCaPs). Dazu wurde ein Aldehyd-Tag (LCTPSR) an den C-Terminus eines Env-Proteins kloniert, das sich zu stabilen Trimeren zusammenlagert. Das Tag-interne Cystein wird nach der Translation in ein Formylglycin mit einer Aldehydgruppe konvertiert. Dies wurde mittels Massenspektrometrie bestätigt. Nach kovalenter Oxim-Ligation der Aldehydgruppe mit einem aminooxy/alkin-Linker, wurde Linker-gebundenes Env in Folge durch eine Click-Reaktion auf der Oberfläche von CaPs immobilisiert. SDS-PAGE-basierte Analysen und CLSM sowie konformationelle ELISAs und Oberflächen-FACS zeigten, dass der Vorgang spezifisch und effizient verläuft und die Env-Konformation erhalten bleibt. Verglichen mit unspezifisch gekoppelten CaPs, führten oCaPs zu besserer B-Zell-Aktivierung in vitro und erhöhten Env-Antikörperspiegeln in vivo. Zusammenfassend zeigt diese Studie die Etablierung einer Nanopartikelplattform für zukünftige Impfstoffstudien und diagnostische Anwendungen mit Bezug auf verschiedenste pathogene Erreger

Dissecting the CHES 2018 AES Challenge

One challenge of the CHES 2018 side channel contest was to break a masked AES implementation. It was impressively won by Gohr et al. by applying ridge regression to obtain guesses for the hamming weights of the (unmasked) AES key schedule, and then using a SAT solver to brute force search the remaining key space. Template attacks are one of the most common approaches used to assess the leakage of a device in a security evaluation. Hence, this raises the question whether ridge regression is a more suitable choice for security evaluation, especially w.r.t. portability. We investigate the feasibility of template attacks to break the presented AES implementation, analyze the leakage of the device, and based on this mount a template attack on hamming weights of the key expansion. We then use classical key search algorithms to recover the AES key. By analyzing the leakage and applying dimension reduction techniques we are able to compress each trace from 650 000 points to only 30 points that are then used to create the templates. Our experimental results indicate that such classical templates achieve similar results compared to ridge regression, and in several cases even slightly outperforming it. According to the organizers, the CTF was aimed to evaluate the concepts of deep learning and classic profiling. Our final conclusion is that the challenge traces are not optimal to settle the question intended, as the leakage is very strong and local. Therefore it is very suitable to apply classical machine learning techniques such as template attacks or ridge regression, and the difficulty in recovering the key is more linked to the resulting key search problem than to the actual attack

Calcium Phosphate Nanoparticle-Based Vaccines as a Platform for Improvement of HIV-1 Env Antibody Responses by Intrastructural Help

Incorporation of immunodominant T-helper epitopes of licensed vaccines into virus-like particles (VLP) allows to harness T-helper cells induced by the licensed vaccines to provide intrastructural help (ISH) for B-cell responses against the surface proteins of the VLPs. To explore whether ISH could also improve antibody responses to calcium phosphate (CaP) nanoparticle vaccines we loaded the nanoparticle core with a universal T-helper epitope of Tetanus toxoid (p30) and functionalized the surface of CaP nanoparticles with stabilized trimers of the HIV-1 envelope (Env) resulting in Env-CaP-p30 nanoparticles. In contrast to soluble Env trimers, Env containing CaP nanoparticles induced activation of naïve Env-specific B-cells in vitro. Mice previously vaccinated against Tetanus raised stronger humoral immune responses against Env after immunization with Env-CaP-p30 than mice not vaccinated against Tetanus. The enhancing effect of ISH on anti-Env antibody levels was not attended with increased Env-specific IFN-γ CD4 T-cell responses that otherwise may potentially influence the susceptibility to HIV-1 infection. Thus, CaP nanoparticles functionalized with stabilized HIV-1 Env trimers and heterologous T-helper epitopes are able to recruit heterologous T-helper cells induced by a licensed vaccine and improve anti-Env antibody responses by intrastructural help

Lower-limb internal loading and potential consequences for fracture healing

Introduction: Mechanical loading is known to determine the course of bone fracture healing. We hypothesise that lower limb long bone loading differs with knee flexion angle during walking and frontal knee alignment, which affects fracture healing success. Materials and methods: Using our musculoskeletal in silico modelling constrained against in vivo data from patients with instrumented knee implants allowed us to assess internal loads in femur and tibia. These internal forces were associated with the clinical outcome of fracture healing in a relevant cohort of 178 extra-articular femur and tibia fractures in patients using a retrospective approach. Results: Mean peak forces differed with femoral compression (1,330-1,936 N at mid-shaft) amounting to about half of tibial compression (2,299-5,224 N). Mean peak bending moments in the frontal plane were greater in the femur (71-130 Nm) than in the tibia (from 26 to 43 Nm), each increasing proximally. Bending in the sagittal plane showed smaller mean peak bending moments in the femur (-38 to 43 Nm) reaching substantially higher values in the tibia (-63 to -175 Nm) with a peak proximally. Peak torsional moments had opposite directions for the femur (-13 to -40 Nm) versus tibia (15-48 Nm) with an increase towards the proximal end in both. Femoral fractures showed significantly lower scores in the modified Radiological Union Scale for Tibia (mRUST) at last follow-up (p < 0.001) compared to tibial fractures. Specifically, compression (r = 0.304), sagittal bending (r = 0.259), and frontal bending (r = -0.318) showed strong associations (p < 0.001) to mRUST at last follow-up. This was not the case for age, body weight, or localisation alone. Discussion: This study showed that moments in femur and tibia tend to decrease towards their distal ends. Tibial load components were influenced by knee flexion angle, especially at push-off, while static frontal alignment played a smaller role. Our results indicate that femur and tibia are loaded differently and thus require adapted fracture fixation considering load components rather than just overall load level

A light-weight NO2 to NOx conversion model for quantifying NOx emissions of point sources from NO2 satellite observations

Nitrogen oxides (NOx = NO + NO2) are air pollutants which are co-emitted with CO2 during high-temperature combustion processes. Monitoring NOx emissions is crucial for assessing air quality and for providing proxy estimates of CO2 emissions. Satellite observations, such as those from the TROPOspheric Monitoring Instrument (TROPOMI) on board the Sentinel-5P satellite, provide global coverage at high temporal resolution. However, satellites measure only NO2, necessitating a conversion to NOx. Previous studies applied a constant NO2-to-NOx conversion factor. In this paper, we develop a more realistic model for NO2 to NOx conversion and apply it to TROPOMI data of 2020 and 2021. To achieve this, we analysed plume-resolving simulations from the MicroHH Large Eddy Simulation model with chemistry for the power plants Bełchatów (PL), Jänschwalde (DE), Matimba and Medupi (ZA), as well as a metallurgical plant in Lipetsk (RU). We used the cross-sectional flux method to calculate NO, NO2, and NOx line densities from simulated NO and NO2 columns and derived NO2-to-NOx conversion factors as a function of the time since emission. Since the method of converting NO2 to NOx presented in this paper assumes steady-state conditions as well as that the conversion factors can be modeled by a negative exponential function, we validated the conversion factors using the same MicroHH data. Finally, we applied the derived conversion factors to TROPOMI NO2 observations of the same sources. The validation of the NO2-to-NOx conversion factors shows that they can account for the NOx chemistry in plumes, in particular for the conversion between NO and NO2 near the source and for the chemical loss of NOx further downstream. When applying these time-since-emission-dependent conversion factors, biases in NOx emissions estimated from TROPOMI NO2 images are greatly reduced from between -50 and -42 % to only -9.5 to -0.5 % in comparison with reported emissions. Single-overpass estimates can be quantified with an uncertainty of 20–27 %, while annual NOx emission estimates have uncertainties in the range of 4–21 % but are highly dependent on the number of successful retrievals. Although more simulations covering a wider range of meteorological and trace gas background conditions will be needed to generalize the approach, this study marks an important step towards a global, uniform, high-resolution, and near real-time estimation of NOx emissions – especially with regard to upcoming NO2 monitoring satellites such as Sentinel-4 and -5 and CO2M

Studying boundary layer methane isotopy and vertical mixing processes at a rewetted peatland site using an unmanned aircraft system

The combination of two well-established methods, of quadrocopter-borne air sampling and methane isotopic analyses, is applied to determine the source process of methane at different altitudes and to study mixing processes. A proof-of-concept study was performed to demonstrate the capabilities of quadrocopter air sampling for subsequently analysing the methane isotopic composition δ13C in the laboratory. The advantage of the system compared to classical sampling on the ground and at tall towers is the flexibility concerning sampling location, and in particular the flexible choice of sampling altitude, allowing the study of the layering and mixing of air masses with potentially different spatial origin of air masses and methane. Boundary layer mixing processes and the methane isotopic composition were studied at Polder Zarnekow in Mecklenburg–West Pomerania in the north-east of Germany, which has become a strong source of biogenically produced methane after rewetting the drained and degraded peatland. Methane fluxes are measured continuously at the site. They show high emissions from May to September, and a strong diurnal variability. For two case studies on 23 May and 5 September 2018, vertical profiles of temperature and humidity were recorded up to an altitude of 650 and 1000 m, respectively, during the morning transition. Air samples were taken at different altitudes and analysed in the laboratory for methane isotopic composition. The values showed a different isotopic composition in the vertical distribution during stable conditions in the morning (delta values of −51.5 ‰ below the temperature inversion at an altitude of 150 m on 23 May 2018 and at an altitude of 50 m on 5 September 2018, delta values of −50.1 ‰ above). After the onset of turbulent mixing, the isotopic composition was the same throughout the vertical column with a mean delta value of −49.9 ± 0.45 ‰. The systematically more negative delta values occurred only as long as the nocturnal temperature inversion was present. During the September study, water samples were analysed as well for methane concentration and isotopic composition in order to provide a link between surface and atmosphere. The water samples reveal high variability on horizontal scales of a few tens of metres for this particular case. The airborne sampling system and consecutive analysis chain were shown to provide reliable and reproducible results for two samples obtained simultaneously. The method presents a powerful tool for distinguishing the source process of methane at different altitudes. The isotopic composition showed clearly depleted delta values directly above a biological methane source when vertical mixing was hampered by a temperature inversion, and different delta values above, where the air masses originate from a different footprint area. The vertical distribution of methane isotopic composition can serve as tracer for mixing processes of methane within the atmospheric boundary layer

Methodology for the characterization and understanding of longitudinal wrinkling during calendering of lithium-ion and sodium-ion battery electrodes

"The manufacturing of lithium-ion battery (LIB) cells is following a complex process chain in which the individual process steps influence the subsequent ones. Meanwhile, increasing requirements especially concerning the battery performance, sustainability and costs are forcing the development of innovative battery materials, production technologies and battery designs. The calendering process directly affects the volumetric energy density of an electrode and therefore of a battery cell. Calendering is still challenging as it causes high stresses in the electrode that lead to defects and thus increased rejection rates. The interaction between electrode material and process as well as the formation of defects is still not fully understood, especially when new material systems are used. In this context, the sodium-ion battery (SIB) is one post-lithium battery system that is a promising option to overcome the limitations of conventional LIBs. Therefore, this paper presents a first material and machine independent methodology to describe and understand the defect type longitudinal wrinkle, which mostly appears at the uncoated current collector edge of an electrode and in running direction. The aim is to systematically characterize the longitudinal wrinkles according to their geometry. The automatic data acquisition is carried out with a laser triangulation system and a 3D scanning system. The geometry values are calculated from the raw data and correlated to selected process parameters. The methodology is applicable regardless of the material as shown by exemplary results of NMC811 cathodes for LIB and hard carbon anodes for SIB. By using two different pilot calenders it is shown, that the data acquisition can be carried out independently of the machine. The presented methodology contributes to finding solutions for the avoidance of longitudinal wrinkling in any battery electrode and therefore to reducing the rejection rate.

Mapping the spatial distribution of NO2 with in situ and remote sensing instruments during the Munich NO2 imaging campaign

We present results from the Munich Nitrogen dioxide (NO2) Imaging Campaign (MuNIC), where NO2 near-surface concentrations (NSCs) and vertical column densities (VCDs) were measured with stationary, mobile, and airborne in situ and remote sensing instruments in Munich, Germany. The most intensive day of the campaign was 7 July 2016, when the NO2 VCD field was mapped with the Airborne Prism Experiment (APEX) imaging spectrometer. The spatial distribution of APEX VCDs was rather smooth, with a horizontal gradient between lower values upwind and higher values downwind of the city center. The NO2 map had no pronounced source signatures except for the plumes of two combined heat and power (CHP) plants. The APEX VCDs have a fair correlation with mobile multi-axis differential optical absorption spectroscopy (MAX-DOAS) observations from two vehicles conducted on the same afternoon (r=0.55). In contrast to the VCDs, mobile NSC measurements revealed high spatial and temporal variability along the roads, with the highest values in congested areas and tunnels. The NOx emissions of the two CHP plants were estimated from the APEX observations using a mass-balance approach. The NOx emission estimates are consistent with CO2 emissions determined from two ground-based Fourier transform infrared (FTIR) instruments operated near one CHP plant. The estimates are higher than the reported emissions but are probably overestimated because the uncertainties are large, as conditions were unstable and convective with low and highly variable wind speeds. Under such conditions, the application of mass-balance approaches is problematic because they assume steady-state conditions. We conclude that airborne imaging spectrometers are well suited for mapping the spatial distribution of NO2 VCDs over large areas. The emission plumes of point sources can be detected in the APEX observations, but accurate flow fields are essential for estimating emissions with sufficient accuracy. The application of airborne imaging spectrometers for studying NSCs is less straightforward and requires us to account for the non-trivial relationship between VCDs and NSCs

Conjugation of Native-Like HIV-1 Envelope Trimers onto Liposomes Using EDC/Sulfo-NHS Chemistry: Requirements and Limitations

The display of native-like human immunodeficiency virus type 1 envelope (HIV-1 Env) trimers on liposomes has gained wide attention over the last few years. Currently, available methods have enabled the preparation of Env-liposome conjugates of unprecedented quality. However, these protocols require the Env trimer to be tagged and/or to carry a specific functional group. For this reason, we have investigated N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide/N-Hydroxysulfosuccinimide (EDC/Sulfo-NHS) chemistry for its potential to covalently conjugate tag-free, non-functionalized native-like Env trimers onto the surface of carboxyl-functionalized liposomes. The preservation of the liposome’s physical integrity and the immunogen’s conformation required a fine-tuned two-step approach based on the controlled use of β-mercaptoethanol. The display of Env trimers was strictly limited to activated liposomes of positive charge, i.e., liposomes with a positive zeta potential that carry amine-reactive Sulfo-NHS esters on their surface. In agreement with that, conjugation was found to be highly ionic strength- and pH-dependent. Overall, we have identified electrostatic pre-concentration (i.e., close proximity between negatively charged Env trimers and positively charged liposomes established through electrostatic attraction) to be crucial for conjugation reactions to proceed. The present study highlights the requirements and limitations of potentially scalable EDC/Sulfo-NHS-based approaches and represents a solid basis for further research into the controlled conjugation of tag-free, non-functionalized native-like Env trimers on the surface of liposomes, and other nanoparticles