Self-Sensing Polymer Composite: White-Light-Illuminated Reinforcing Fibreglass Bundle for Deformation Monitoring

The goal of our research was to develop a continuous glass fibre-reinforced epoxy matrix self-sensing composite. A fibre bundle arbitrarily chosen from the reinforcing glass fabric in the composite was prepared to guide white light. The power of the light transmitted by the fibres changes as a result of tensile loading. In our research, we show that a selected fibre bundle even without any special preparation can be used as a sensor to detect deformation even before the composite structure is damaged (before fibre breaking)

Determination of 24 primary aromatic amines in aqueous food simulants by combining solid phase extraction and salting-out assisted liquid?liquid extraction with liquid chromatography tandem mass spectrometry

Carcinogenic primary aromatic amines (PAAs) can be released from improperly manufactured food packaging materials. The limit for the sum of PAAs is set to 10 ?gkg- 1 in Commission Regulation No. 10/2011 (FCM Regulation). However, a lower individual limit, 2 ?gkg- 1 has been recently introduced for the carcinogenic PAAs in Commission Regulation No. 2020/1245. As the majority of the previously published methods are no longer compliant with the current regulation, a UHPLC-MS/MS method was developed to enable food packaging compliance testing for PAAs not only from 3% (w/v) acetic acid, but also from 10% (v/v) ethanol food simulant. Since the latest amendment of the FCM Regulation refers to the list of the 22 restricted PAAs of EU Regulation No. 1907/2006, these PAAs were selected as target compounds along with aniline and p-toluidine, the most common impurities of azo colorants and isocyanates. An enrichment factor of 20 could be achieved combining solid phase extraction with salting-out assisted liquid?liquid extraction. The method was successfully validated and applied on real samples. Limit of quantitation (LOQ) and limit of detection (LOD) values were 0.15 ?gL-1 and 0.05 ?gL-1 for both food simulants, respectively; except for 2,4-diaminotoluene, aniline and 4,4?-oxydianiline. However, even these compounds had lower LOD values than the new individual limit of 2 ?gkg- 1. Cumulative LOD values for both food simulants (1.6 ?gL-1 and 1.5 ?gL-1 for 3% (w/v) acetic acid and 10% (v/v) ethanol, respectively) were lower than the 10 ?gkg- 1 specified in the FCM Regulation. Accuracy values were between 70 and 118% for both food simulants for the majority of PAAs. Both within-day and between-day precision values were below 20%. This method proved to be suitable for daily routine analysis enabling compliance testing of food packaging materials according to the latest regulations. The method was successfully applied for the analysis of plastic kitchenware samples

Intelligent image-based in situ single-cell isolation

Quantifying heterogeneities within cell populations is important for many fields including cancer research and neurobiology; however, techniques to isolate individual cells are limited. Here, we describe a high-throughput, non-disruptive, and cost-effective isolation method that is capable of capturing individually targeted cells using widely available techniques. Using high-resolution microscopy, laser microcapture microscopy, image analysis, and machine learning, our technology enables scalable molecular genetic analysis of single cells, targetable by morphology or location within the sample.Peer reviewe

Some gating potentiators, including VX-770, diminish ΔF508-CFTR functional expression.

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane regulator (CFTR) that result in reduced anion conductance at the apical membrane of secretory epithelia. Treatment of CF patients carrying the G551D gating mutation with the potentiator VX-770 (ivacaftor) largely restores channel activity and has shown substantial clinical benefit. However, most CF patients carry the ΔF508 mutation, which impairs CFTR folding, processing, function, and stability. Studies in homozygous ΔF508 CF patients indicated little clinical benefit of monotherapy with the investigational corrector VX-809 (lumacaftor) or VX-770, whereas combination clinical trials show limited but significant improvements in lung function. We show that VX-770, as well as most other potentiators, reduces the correction efficacy of VX-809 and another investigational corrector, VX-661. To mimic the administration of VX-770 alone or in combination with VX-809, we examined its long-term effect in immortalized and primary human respiratory epithelia. VX-770 diminished the folding efficiency and the metabolic stability of ΔF508-CFTR at the endoplasmic reticulum (ER) and post-ER compartments, respectively, causing reduced cell surface ΔF508-CFTR density and function. VX-770-induced destabilization of ΔF508-CFTR was influenced by second-site suppressor mutations of the folding defect and was prevented by stabilization of the nucleotide-binding domain 1 (NBD1)-NBD2 interface. The reduced correction efficiency of ΔF508-CFTR, as well as of two other processing mutations in the presence of VX-770, suggests the need for further optimization of potentiators to maximize the clinical benefit of corrector-potentiator combination therapy in CF

3D-Beacons: decreasing the gap between protein sequences and structures through a federated network of protein structure data resources

While scientists can often infer the biological function of proteins from their 3-dimensional quaternary structures, the gap between the number of known protein sequences and their experimentally determined structures keeps increasing. A potential solution to this problem is presented by ever more sophisticated computational protein modeling approaches. While often powerful on their own, most methods have strengths and weaknesses. Therefore, it benefits researchers to examine models from various model providers and perform comparative analysis to identify what models can best address their specific use cases. To make data from a large array of model providers more easily accessible to the broader scientific community, we established 3D-Beacons, a collaborative initiative to create a federated network with unified data access mechanisms. The 3D-Beacons Network allows researchers to collate coordinate files and metadata for experimentally determined and theoretical protein models from state-of-the-art and specialist model providers and also from the Protein Data Bank

Subtype-specific KRAS mutations in advanced lung adenocarcinoma: A retrospective study of patients treated with platinum-based chemotherapy

Background: Platinum-based chemotherapy is the most common treatment in advanced-stage lung adenocarcinoma. Because the clinical significance of KRAS mutational status in this setting has not yet been clearly determined, a mutation subtype-specific analysis was performed in the so far largest cohort of Caucasian patients with KRAS mutant advanced-stage lung adenocarcinoma treated with platinum-based chemotherapy. Methods: 505 Caucasian stage III-IV lung adenocarcinoma patients with known amino acid substitution-specific KRAS mutational status and treated with platinum-based chemotherapy were included. The correlations of subtype-specific KRAS mutations with smoking status, progression-free and overall survival (PFS and OS, respectively) and therapeutic response were analysed. Results: Among 338 KRAS wild-type, 147 codon 12 mutant and 20 codon 13 mutant patients, there were no mutation-related significant differences in PFS or OS (P values were 0.534 and 0.917, respectively). Eastern Cooperative Oncology Group (ECOG) status and clinical stage were significant independent prognostic factors. KRAS mutation showed a significant correlation with smoking status (P = 0.018). Importantly, however, G12V KRAS mutant patients were significantly more frequent among never-smokers than all other codon 12 KRAS mutant (G12x) subtypes (P = 0.016). Furthermore, this subgroup tended to have a higher response rate (66% versus 47%; P = 0.077). A modestly longer median PFS was also found in the G12V mutant cohort (233 days; versus 175 days in the G12x group; P = 0.145). Conclusions: While KRAS mutation status per se is neither prognostic nor predictive in stage III-IV lung adenocarcinoma, subtype-specific analysis may indeed identify clinically relevant subgroups of patients that may ultimately influence treatment decisions. © 2014 The Authors

Implementing the Defense Resource Management model in emerging democracies

This thesis examines the political organizational and cultural barriers to the implementation of the U.S. Defense Resource Management Model (DRMM) decision support system by the Ministry of Defense in Hungary between 1995 and 2000. It surveys the heritage of the Warsaw Pact alliance on military planning in Hungary prior to 1989. A detailed description of the DRMM system is provided along with an implementation history of DRMM in Hungary. Factors in the implementation failure are examined and suggestions are offered for improving the management of software and systems implementation in the future.http://archive.org/details/implementingdefe109451100

Comprehensive Collection and Prediction of ABC Transmembrane Protein Structures in the AI Era of Structural Biology

The number of unique transmembrane (TM) protein structures doubled in the last four years, which can be attributed to the revolution of cryo-electron microscopy. In addition, AlphaFold2 (AF2) also provided a large number of predicted structures with high quality. However, if a specific protein family is the subject of a study, collecting the structures of the family members is highly challenging in spite of existing general and protein domain-specific databases. Here, we demonstrate this and assess the applicability and usability of automatic collection and presentation of protein structures via the ABC protein superfamily. Our pipeline identifies and classifies transmembrane ABC protein structures using the PFAM search and also aims to determine their conformational states based on special geometric measures, conftors. Since the AlphaFold database contains structure predictions only for single polypeptide chains, we performed AF2-Multimer predictions for human ABC half transporters functioning as dimers. Our AF2 predictions warn of possibly ambiguous interpretation of some biochemical data regarding interaction partners and call for further experiments and experimental structure determination. We made our predicted ABC protein structures available through a web application, and we joined the 3D-Beacons Network to reach the broader scientific community through platforms such as PDBe-KB