Search

Composites revolutionize material performance, fostering innovation and efficiency in diverse sectors. Elastomer-based polymeric composites are crucial for applications requiring superior mechanical strength and durability. Widely applied in automotives, aerospace, construction, and consumer goods, they excel under extreme conditions. Composites based on recycled rubber, fortified with reinforcing fillers, represent a sustainable material innovation by repurposing discarded rubber. The integration of reinforcing agents enhances the strength and resilience of this composite, and the recycled polymeric matrix offers an eco-friendly alternative to virgin elastomers, reducing their environmental impact. Devulcanized rubber, with inherently lower mechanical properties than virgin rubber, requires enhancement of its quality for reuse in a circular economy: considerable amounts of recycled tire rubber can only be applied in new tires if the property profile comes close to the one of the virgin rubber. To achieve this, model passenger car tire and whole tire rubber granulates were transformed into elastomeric composites through optimized devulcanization and blending with additional fillers like carbon black and silica-silane. These fillers were chosen as they are commonly used in tire compounding, but they lose their reactivity during their service life and the devulcanization process. Incorporation of 20% ( w / w ) additional filler enhanced the strength of the devulcanizate composites by up to 15%. Additionally, increased silane concentration significantly further improved the tensile strength, Payne effect, and dispersion by enhancing the polymer-filler interaction through improved silanization. Higher silane concentrations reduced elongation at break and increased crosslink density, as it leads to a stable filler-polymer network. The optimal concentration of a silica-silane filler system for a devulcanizate was found to be 20% silica with 3% silane, showing the best property profile.

Vesicular release of neurotransmitters and hormones relies on the dynamic assembly of the exocytosis/trans-SNARE complex through sequential interactions of synaptobrevins, syntaxins, and SNAP-25. Despite SNARE-mediated release being fundamental for intercellular communication in all excitable tissues, the role of auxiliary proteins modulating the import of reserve vesicles to the active zone, and thus, scaling repetitive exocytosis remains less explored. Secretagogin is a Ca 2+ -sensor protein with SNAP-25 being its only known interacting partner. SNAP-25 anchors readily releasable vesicles within the active zone, thus being instrumental for 1st phase release. However, genetic deletion of secretagogin impedes 2nd phase release instead, calling for the existence of alternative protein-protein interactions. Here, we screened the secretagogin interactome in the brain and pancreas, and found syntaxin-4 grossly overrepresented. Ca 2+ -loaded secretagogin interacted with syntaxin-4 at nanomolar affinity and 1:1 stoichiometry. Crystal structures of the protein complexes revealed a hydrophobic groove in secretagogin for the binding of syntaxin-4. This groove was also used to bind SNAP-25. In mixtures of equimolar recombinant proteins, SNAP-25 was sequestered by secretagogin in competition with syntaxin-4. K d differences suggested that secretagogin could shape unidirectional vesicle movement by sequential interactions, a hypothesis supported by in vitro biological data. This mechanism could facilitate the movement of transport vesicles toward release sites, particularly in the endocrine pancreas where secretagogin, SNAP-25, and syntaxin-4 coexist in both α- and β-cells. Thus, secretagogin could modulate the pace and fidelity of vesicular hormone release by differential protein interactions., Competing Interests: Competing interests statement:T.G.M.H. has stocks in Lundbeck A/S. All other authors declare that they have no conflict of interest.

Objective: The article tackles various issues arising in the context of the process of digitalization in the health sector. The communication and availability of health data, health registers, the electronic health record, consent procedures for the transfer of data and access to health data for research are considered., Methods: The study is based on a computer-assisted telephone survey (dual-frame) of a random sample of adult people living in Germany. Data was collected in the period between June 01 and June 27, 2022 (n = 1,308)., Results: The level of knowledge concerning the transmission of health data to health insurers is good, whereas the existence of central death-, vaccination- and health registers as well as the access to health data by treating physicians is overestimated. The general acceptance of medical registers is very high. Half the population is unfamiliar with the electronic health record, and the willingness to use it is rather low. An opt-in procedure is preferred when transferring data, and more than eighty percent would release data in their electronic health file for research purposes. Three quarters would consent that their health data be handed over to general research, especially if reserach facilities were situated at German universities, under the condition that their data be treated confidentiallly. The willingness to release data correlates with the level of trust in the press as well as in universities and colleges and decreases when a data leak is considered to be serious., Discussion and Conclusion: In Germany, as in other European countries, we observe a great willingness of people to release health data for research purposes. However, the propensity to use the electronic health file is comparatively low, as is the acceptance of an opt-out procedure, which in the literature is considered a prerequisite for the successful implementation of electronic health records in other countries. Unsurprisingly, a general trust in research and government agencies that process health data is a key factor., (Copyright © 2023. Published by Elsevier GmbH.)

Most general population web surveys are based on online panels maintained by commercial survey agencies. Many of these panels are based on non-probability samples. However, survey agencies differ in their panel selection and management strategies. Little is known if these different strategies cause differences in survey estimates. This paper presents the results of a systematic study designed to analyze the differences in web survey results between agencies. Six different survey agencies were commissioned with the same web survey using an identical standardized questionnaire covering factual health items. Five surveys were fielded at the same time. A calibration approach was used to control the effect of demographics on the outcome. Overall, the results show differences between probability and non-probability surveys in health estimates, which were reduced but not eliminated by weighting. Furthermore, the differences between non-probability surveys before and after weighting are larger than expected between random samples from the same population., (© 2024. The Author(s).)

The study is based on a German single-topic population survey on vaccination willingness against COVID-19 (VWC) by the authors (2020, n = 2014). The single-topic survey allowed us to test several competing explanations for VWC, as discussed in the literature. The VWC in the sample was 67.3%. Logistic regression was used to identify factors affecting VWC. Being at high risk from COVID-19 and having received flu vaccination have a positive impact on VWC. Perceived VWC of friends has a strong positive effect on respondents' VWC. Bivariate relationships of gender, age, and level of education with VWC were no longer significant in a multivariate analysis. Trust in alternative medicine and belief in conspiracy theories have a negative effect on VWC., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The project is funded by the Bavarian State Ministry of Science and the Arts as part of the Regensburg Center of Health Sciences and Technology (RCHST) at the Ostbayerische Technische Hochschule Regensburg (OTH Regensburg). Open Access publication is funded by OTH Regensburg. The sponsor was not involved in data collection, data analysis nor in any stage of the submission process., (© 2023 The Authors.)

The disposal of tires at the end of their lifespan results in societal and environmental issues. To tackle this, recycling and reuse are effective solutions. Among various recycling methods, devulcanization is considered to be a very sustainable option, as it involves the controlled breakdown of crosslinks while maintaining the polymer backbones. The objective of this study is to develop a sustainable devulcanization process for passenger car tire rubber using silanes. In this study, a thermo-mechanical-chemical devulcanization process was conducted to screen six potential devulcanization aids (DAs). Silanes were chosen as they are widely used in tire rubber as coupling agents for silica. The efficiency of the devulcanization was studied by the degree of network breakdown, miscibility of the devulcanized material, and mechanical properties of the de- and revulcanized material. Compared to the parent compound, a 55-60% network breakdown was achieved for the devulcanizate along with 50-55% of tensile strength recovery. In addition to superior devulcanization efficiency, this DA offers a sustainable alternative to the conventional ones, such as di-phenyl-di-sulphide, due to its compliance with safety regulations. The devulcanizate can be utilized in high-performance applications, such as tires and seals, while 100% devulcanizate can be employed in low-strength technical rubber products.

Pseudouridimycin is a microbial C -nucleoside natural product that specifically inhibits bacterial RNA polymerases by binding to the active site and competing with uridine triphosphate for the nucleoside triphosphate (NTP) addition site. Pseudouridimycin consists of 5'-aminopseudouridine and formamidinylated, N-hydroxylated Gly-Gln dipeptide moieties to allow Watson-Crick base pairing and to mimic protein-ligand interactions of the triphosphates of NTP, respectively. The metabolic pathway of pseudouridimycin has been studied in Streptomyces species, but no biosynthetic steps have been characterized biochemically. Here, we show that the flavin-dependent oxidase SapB functions as a gate-keeper enzyme selecting pseudouridine ( K M = 34 μM) over uridine ( K M = 901 μM) in the formation of pseudouridine aldehyde. The pyridoxal phosphate (PLP)-dependent SapH catalyzes transamination, resulting in 5'-aminopseudouridine with a preference for arginine, methionine, or phenylalanine as cosubstrates as amino group donors. The binary structure of SapH in complex with pyridoxamine-5'-phosphate and site-directed mutagenesis identified Lys289 and Trp32 as key residues for catalysis and substrate binding, respectively. The related C -nucleoside oxazinomycin was accepted as a substrate by SapB with moderate affinity ( K M = 181 μM) and was further converted by SapH, which opens possibilities for metabolic engineering to generate hybrid C -nucleoside pseudouridimycin analogues in Streptomyces .

Introduction: Population wide educational attainment registers are necessary for educational planning and research. Regular linking of databases is needed to build and update such a register. Without availability of unique national identification numbers, record linkage must be based on quasi-identifiers such as name, date of birth and sex. However, the data protection principle of data minimization aims to minimize the set of identifiers in databases., Objectives: Therefore, the German Federal Ministry of Research and Education commissioned a study to inform legislation on the minimum set of identifiers required for a national educational register., Methods: To justify our recommendations empirically, we implemented a microsimulation of about 20 million people. The simulated register accumulates changes and errors in identifiers due to migration, regional mobility, marriage, school career and mortality, thereby allowing the study of errors on longitudinal datasets. Updated records were linked yearly to the simulated register using several linkage methods. Clear-text methods as well as privacy-preserving (PPRL) methods were compared., Results: The results indicate linkage bias if only the primary identifiers are available in the register. More detailed identifiers, including place of birth, are required to minimize linkage bias. The amount of information available to identify a person for matching is more critical for linkage quality than the record linkage method applied. Differences in linkage quality between the best procedures (probabilistic linkage and multiple matchkeys) are minor., Conclusions: Microsimulation is a valuable tool for designing record linkage procedures. By modelling the processes resulting in changes or errors in quasi-identifiers, predicting data quality to be expected after the implementation of a register seems possible., Competing Interests: Statement on conflicts of interest: The authors declare no conflicts of interest.

Databases covering all individuals of a population are increasingly used for research and decision-making. The massive size of such databases is often mistaken as a guarantee for valid inferences. However, population data have characteristics that make them challenging to use. Various assumptions on population coverage and data quality are commonly made, including how such data were captured and what types of processing have been applied to them. Furthermore, the full potential of population data can often only be unlocked when such data are linked to other databases. Record linkage often implies subtle technical problems, which are easily missed. We discuss a diverse range of myths and misconceptions relevant for anybody capturing, processing, linking, or analysing population data. Remarkably, many of these myths and misconceptions are due to the social nature of data collections and are therefore missed by purely technical accounts of data processing. Many are also not well documented in scientific publications. We conclude with a set of recommendations for using population data., Competing Interests: Statement on conflicts of interest: The authors have no conflicts of interest.

Linking several databases containing information on the same person is an essential step of many data workflows. Due to the potential sensitivity of the data, the identity of the persons should be kept private. Privacy-Preserving Record-Linkage (PPRL) techniques have been developed to link persons despite errors in the identifiers used to link the databases without violating their privacy. The basic approach is to use encoded quasi-identifiers instead of plain quasi-identifiers for making the linkage decision. Ideally, the encoded quasi-identifiers should prevent re-identification but still allow for a good linkage quality. While several PPRL techniques have been proposed so far, Bloom filter-based PPRL schemes (BF-PPRL) are among the most popular due to their scalability. However, a recently proposed attack on BF-PPRL based on graph similarities seems to allow individuals' re-identification from encoded quasi-identifiers. Therefore, the graph matching attack is widely considered a serious threat to many PPRL-approaches and leads to the situation that BF-PPRL schemes are rejected as being insecure. In this work, we argue that this view is not fully justified. We show by experiments that the success of graph matching attacks requires a high overlap between encoded and plain records used for the attack. As soon as this condition is not fulfilled, the success rate sharply decreases and renders the attacks hardly effective. This necessary condition does severely limit the applicability of these attacks in practice and also allows for simple but effective countermeasures., Competing Interests: The authors have declared that no competing interests exist.

Background: In breast cancer and prostate cancer patients, bone metastases (BM) present the main cause of morbidity and often cause debilitating pain, impaired functioning and subsequent deterioration of quality of life (QoL). The management of BM is still challenging. Maintenance or improvement in QoL is the main goal of treatment. Antiresorptive treatment, such as denosumab and bisphosphonates, can help to reduce the frequency of skeletal complications, to control bone pain and potentially to improve QoL. The optimal time point for initiation of antiresorptive therapy is still discussed controversially. In patients with BM, bone pain can be used as a surrogate measure of QoL. However, limited data exist on health-related QoL in patients with BM under antiresorptive treatment. The PROBone registry study evaluated complaints and limitations caused by BM of breast and prostate cancer patients using patient-reported outcomes (PROs) in real-world in Germany., Methods: Between 2014 and 2019, 500 patients with histological confirmation of advanced breast or prostate cancer, diagnosed with BM at start of their first antiresorptive therapy were prospectively enrolled in 65 outpatient-centers specialized in medical oncology across Germany. Changes of QoL were assessed monthly from baseline until a maximum of 12 months using the validated pain score Functional Assessment of Cancer Therapy Quality of Life Measurement in patients with bone pain (FACT-BP) supplemented by questions on general pain and on the impact of time spent for treatment of illness on patients' daily activities. Statistical analysis was performed descriptively by relative and absolute frequencies., Results: In total, 486 patients were eligible for final analysis, of these 310 were diagnosed with breast cancer and 176 with prostate cancer. Median age was 67 years for breast cancer and 76 years for prostate cancer patients. 79.7% of breast cancer and 59.7% of prostate patients started antiresorptive treatment within 3 months after diagnosis of BM. More than 75% of patients suffered from bone pain at study inclusion. In total 52% of breast cancer patients and 47.9% of prostate cancer patients reported to take pain medication during the observation period. In breast and prostate cancer patients an initial pain reduction after start of BTA was observed: General pain and bone pain levels as well as the median FACT-BP score showed a constant improvement over the first months and maintained stable at a constant level afterwards. Subgroup analysis showed that patients without pain at baseline reported distinctly better FACT-BP scores throughout the whole observation period than patients with pain at baseline. Looking at time-stress (M)-scores, younger breast cancer patients (<65 years) showed highest burden especially during the first months of treatment., Conclusions: Our results indicate overall good adherence to current guideline recommendation, with most breast and prostate cancer patients starting antiresorptive therapy within the first 3 months after diagnosis of BM. This point gains even more importance as our data support current recommendations by ESMO guidelines as well as by German evidence-based S3-guidelines for diagnosis and treatment of breast and prostate cancer to initiate bone-targeted agents (BTA) as soon as BM are diagnosed, to keep pain levels at the lowest level possible, to minimize the debilitating effects of metastatic bone pain and maintain a good QoL. Bone pain management by an early use of BTA following BM diagnosis might improve patient care., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 iOMEDICO AG.)

Our previous studies on FabG have identified two compounds 5-bromo-2-(thiophene-2-carboxamido) benzoic acid (A) and ethyl 6-bromo-2-((dimethylamino)methyl)-5-hydroxy-1-phenyl-1H-indole-3-carboxylate(B) as best hits with allosteric mode of inhibition. FabG is an integral part of bacterial fatty acid biosynthetic system FAS II shown to be an essential gene in most ESKAPE Pathogens. The current work is focussed on lead expansion of these two hit molecules which ended up with forty-three analogues (twenty-nine analogues from lead compound A and fourteen compounds from lead compound B). The enzyme inhibition studies revealed that compound 15 (effective against EcFabG, AbFabG, StFabG, MtFabG1) and 19 (inhibiting EcFabG and StFabG) had potency of broad-spectrum inhibition on FabG panel., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Masson SAS.)

In the present study, steady numerical simulations performed on the counter rotating turbo fan (CRTF) COBRA are compared with experimental data carried at the CIAM C-3A test-bench in Moscow. For this purpose, a systematic analysis of the measurement uncertainties was performed for the global aerodynamic performances of the CRTF, namely, the massflow, the total pressure ratio, the isentropic efficiency, as well as the torque ratio applied on both fan rows. Several numerical models are investigated to highlight their effects on the aforementioned predicted quantities. Differences in modeling consist in grid resolutions and the use of two turbulence models popular in the turbomachinery community. To match as much as possible the experiment running conditions, the performance map of the CRTF is simulated using the exact measured speed ratio and massflow. The comparisons show good estimations of the numerical simulation over the entire performance map. The main differences between the turbulence models occur at part-speed close to stall conditions. More surprisingly at aerodynamic design point, the importance of the turbulence modeling on the predicted torque ratio has been pointed out., (© The Author(s) 2021.)