Longitudinal Multimodal Transformer Integrating Imaging and Latent Clinical Signatures From Routine EHRs for Pulmonary Nodule Classification

The accuracy of predictive models for solitary pulmonary nodule (SPN) diagnosis can be greatly increased by incorporating repeat imaging and medical context, such as electronic health records (EHRs). However, clinically routine modalities such as imaging and diagnostic codes can be asynchronous and irregularly sampled over different time scales which are obstacles to longitudinal multimodal learning. In this work, we propose a transformer-based multimodal strategy to integrate repeat imaging with longitudinal clinical signatures from routinely collected EHRs for SPN classification. We perform unsupervised disentanglement of latent clinical signatures and leverage time-distance scaled self-attention to jointly learn from clinical signatures expressions and chest computed tomography (CT) scans. Our classifier is pretrained on 2,668 scans from a public dataset and 1,149 subjects with longitudinal chest CTs, billing codes, medications, and laboratory tests from EHRs of our home institution. Evaluation on 227 subjects with challenging SPNs revealed a significant AUC improvement over a longitudinal multimodal baseline (0.824 vs 0.752 AUC), as well as improvements over a single cross-section multimodal scenario (0.809 AUC) and a longitudinal imaging-only scenario (0.741 AUC). This work demonstrates significant advantages with a novel approach for co-learning longitudinal imaging and non-imaging phenotypes with transformers

General and microRNA-mediated mRNA degradation occurs on ribosome complexes in Drosophila cells

Post-transkriptionelle Prozesse wie mRNA-Abbau, mRNA-Kontrolle, Proteinsynthese und ihre Repression sowie die miRNA- oder siRNA-vermittelte Genkontrolle spielen eine entscheidende Rolle bei der Regulation der Genexpression. Die Prozesse sinddurch viele verschiedene Faktoren stark reguliert. Neben der Verwendung einiger gemeinsamer Proteinfaktoren scheinen die Prozesse auch physisch eng aneinander gekoppelt zu sein. Dies ist beispielsweise für die Proteinsynthese und den Abbau von mRNA bekannt. Während deren Mechanismen gut etabliert sind, ist es noch nicht klar wo in der Zelle der mRNA-Abbau lokalisiert ist. Die enge Koppelung von Proteinsynthese undmRNA-Abbau legt die Möglichkeit des Abbaues von mRNAs auf dem Ribosom nahe. Daher war es unser Ziel die Möglichkeit eines mRNA-Abbaus auf dem Ribosom in Drosophila-Zellen, als einen Vertreter höherer Eukaryoten, zu untersuchen. Zuerst verwendeten wir Polysomprofileum die Ko-Migration von HPat, NOT2 und AGO1 mit Polysomen nachzuweisen. Diese Faktoren wurden ausgewählt, da sie Bestandteile in den Komplexen für das Decapping, der Deadenylierung oder die Regulation durch miRNAs sind. In weiterer Folge haben wir die Methode der Ribosomen-Affinitätsreinigung etabliert. Damit konnten wir nachweisen, dass zahlreiche Deadenylierungs- und Decapping Faktoren mit Ribosomenkomplexen assoziiert sind. Interessanterweise waren sowohl AGO1 als auch GW182, zwei Schlüsselfaktoren des miRNA-vermittelten mRNA-Abbauweges, ebenfalls mit Ribosomenkomplexen assoziiert. Wenn die Assoziation von Faktoren mit Ribosomenkomplexen in Gegenwart von RNasen getestet wurde, kam es zu keiner gemeinsamen Aufreinigung. Dies legt nahe, dass die Assoziation der Proteinfaktoren am wahrscheinlichsten mit mRNA und nicht mit Ribosomen erfolgt. Der nächste Schritt bestand darin zu zeigen, dass Abbauzwischenprodukte von mRNAs an den Ribosomenkomplexen nachgewiesen werden können. Es ist uns gelungen mRNA-Abbau-Intermediate aus Ribosomenkomplexen zu isolieren und mittels Hochdurchsatz-Sequenzanalyse zu analysieren. Ungefähr 12 000 mRNAs oder 93% der entkappten mRNA-Fragmente wurden mit der gleichen relativen Häufigkeit auf den Ribosomenkomplexen wie im Zelllysat nachgewiesen Dies zeigt, dass nicht nur einzelne mRNAs sondern die große Mehrzahl der mRNAs an den Ribosomen abgebaut wird. Zusammenfassend weisen unsere Daten auf die Assoziation der meisten mRNAs mit den Ribosomen während ihres Abbaues in Drosophila-Zellen hin. Ein besseres Verständnis des Mechnismus und der Lage von generellem und miRNA-vermitteltem RNA-Abbau kann nicht nur beim Verständnis der Kinetik und Regulation des mRNA-Abbaus helfen, sondern auch beim Verständnis verschiedener zellularer Prozesse, wie zum Beispiel Entwicklung, Differenzierung oder wie biologische Systeme mit all ihrer Komplexität auf externe Stimuli reagieren um stressvolle Situationen zu meistern und zurück zur Homöostase zu finden.Post-transcriptional processes such as mRNA degradation, mRNA surveillance, translation, translation repression, and miRNA or siRNA-mediated gene silencing play crucial roles in the regulation of gene expression. They are highly regulated and targeted by many factors. These processes not only share several protein factors but also appear physically connected. It is well known that translation and mRNA degradation are tightly coupled. While their mechanisms are well established, it is still not completely clear where in the cell mRNA degradation occurs. The close connection between translation and degradation suggests the possibility for mRNA degradation to take place on the ribosome. Therefore, our aim in this study was to investigate the possibility of mRNA degradation on the ribosome in Drosophila cells as a higher Eukaryote. At first, we used polysome profilesto demonstrate the co-migration of HPat, NOT2, and AGO1 with ribosome complexes. These factors were chosen and tested as representatives of the decapping, deadenylation and miRNA complex. Later we have established ribosome affinity purification and we could show the co-purification of numerous deadenylation and decapping factors with ribosome complexes. Interestingly, both AGO1 and GW182, key factors of the miRNA mediated mRNA degradation pathway, were also associated with ribosome complexes. Howevever, the copurification of factors failed in the presence of limiting amounts of RNases. This suggests that the association of factors rather with mRNA then with ribosomes. The next step was to show whether the mRNA-degradation intermediates could be detected on the ribosome complexes and how abundant is the degradation on the ribosomes. We have isolated decapped mRNA-degradation intermediates from ribosome complexes and we have performed high-throughput sequence analysis. Approximately 12.000 mRNAs or 93% of the decapped mRNA fragments were detected at the same relative abundance on the ribosome complexes as in the cell lysate. This showed the great abundance of mRNA degradation on the ribosome. In summary, our data strongly indicate the association of most mRNAs as well as mRNA targeted by miRNAs with the ribosomes during their degradation in Drosophila cells.A better understanding of the mechanism and location of both general and miRNA-mediated degradation of mRNAs will help us improve our understanding of the kinetics of mRNA degradation and its regulation andalso of various cellular processes, such as development, differentiation or how biological systems with all its complexity respond to various external stimuli to overcome the stressful situation and keep its homeostasis

Contactless Temperature Sensing via Luminescence

International Conference on Transparent Optical Networks-ICTON, 18th International Conference on Transparent Optical Networks (ICTON), Jul 10-14, 2016, Univ Trento, Fac Letters and Philosophy, Trento, Ital

Self-referenced luminescence thermometry with Sm3+ doped TiO2 nanoparticles

The performance of Sm3+ doped TiO2 nanoparticles for luminescence temperature sensing was tested over a temperature range from room to 110 degrees C. The Sm3+ ions were incorporated into TiO2 nanocrystals using hydrolytic sol-gel route. Microstructural characterization of the obtained material was performed using transmission electron microscopy and x-ray diffraction measurements. Luminescence emission spectra of Sm3+ doped TiO2 nanoparticles consists of two distinct spectral regions: the high energy region associated with the trap emission of the TiO2 host, and the low energy region with well-resolved emission peaks of the Sm3+ ions. The ratio between Sm3+ emission and TiO2 trap emission shows strong temperature dependence, and is tested for temperature sensing. The relative sensor sensitivity was found to be higher than 1% degrees C-1 over given temperature range with the maximum value of 10.54% degrees C-1 at 57.5 degrees C. Lifetime data derived from the Sm3+ emission decay revealed that time-resolved measurements provide comparable quality of temperature sensing as corresponding ratiometric measurements, with a maximum relative sensitivity of 10.14% degrees C-1 at 66.5 degrees C

White- and blue-light-emitting dysprosium(III) and terbium(III)-doped gadolinium titanate phosphors

Here we report the synthesis and structural, morphological, and photoluminescence analysis of white- and blue-light-emitting Dy3+- and Tm3+-doped Gd2Ti2O7 nanophosphors. Single-phase cubic Gd2Ti2O7 nanopowders consist of compact, dense aggregates of nanoparticles with an average size of similar to 25 nm for Dy3+-doped and similar to 50 nm for Tm3+-doped samples. The photoluminescence results indicated that ultraviolet (UV) light excitation of the Dy3+-doped sample resulted in direct generation of white light, while a dominant yellow emission was obtained under blue-light excitation. Intense blue light was obtained for Tm3+-doped Gd2Ti2O7 under UV excitation suggesting that this material could be used as a blue phosphor

Synthesis and Characterization of Novel Urethane-Siloxane Copolymers with a High Content of PCL-PDMS-PCL Segments

Novel polyurethane copolymers derived from 4,4'-methylenediphenyl diisocyanate (MDI), 1,4-butanediol (BD) and alpha, omega-dihydroxy-[poly(caprolactone)-poly (dimethylsiloxane)-poly(caprolactone)] (a, x-dihydroxy( PCL-PDMS-PCL); (M) over bar (n) 6100 g mol(-1)) were synthesized by a two-step polyaddition reaction in solution. In the synthesis of the polyurethanes, the PCL blocks served as a compatibilizer between the nonpolar PDMS blocks and the polar comonomers, MDI and BD. The synthesis of thermoplastic polyurethanes (TPU) with high soft segment contents was optimized in terms of the concentrations of the reactants, the molar ratio of the NCO/OH groups, and the time and temperature of the polyaddition reaction. The structure, composition, and hard MDI/BD segment length of the synthesized polyurethane copolymers were determined by H-1, C-13-NMR, and two-dimensional correlation (COSY, HSQC, and HMBC) spectroscopy, while the hydrogen bonding interactions in the copolymers were analyzed by FT-IR spectroscopy. The influence of the reaction conditions on the structure, molecular weight, thermal, and some physical properties was studied at constant composition of the reaction mixture. A change in the molar ratio of the NCO/OH groups and the reaction conditions modified not only the molecular weight of the synthesized polyurethanes, but also the microstructure and therefore the thermal and physical properties of the copolymers. It was demonstrated that only PCL segments with high soft segment contents crystallize, thereby showing spherulitic morphology