Somatic genome alterations in relation to age in smoking related cancers

Head and Neck Squamous Cell Carcinoma (HNSCC), Lung Squamous Cell Carcinoma (LUSC) and Lung Adenocarcinoma (LUAD) are among the most common cause of global cancer-related mortality and the common major risk factor is smoking consumption. By analyzing 203 HNSCC, 480 LUSC and 486 LUAD samples from The Cancer Genome Atlas, we systematically studied the mutational load as well as mutational patterns in relation to patient age. Multiple mutational processes appear to be simultaneously operative with various dynamic changes due to the endogenous and exogenous environments, life style habits and physiological ageing. We found a proportional increase, independently of smoking consumption, of the HNSCC mutation frequency rate in relation to the patient age. Therefore, multiple factors might participate to the accumulation of genetic events in the elderly and the prolonged tobacco exposure might increase the ageing-related SNPs burden. On the contrary, LUSC and LUAD showed a higher mutational rate among younger patients. TP53 mutations in younger LUAD patients might be a crucial factor enhancing the sensitivity to smoking related mutations leading to a burst of somatic alterations. Indeed, TP53 mutations and patient age significantly affected the higher mutational rate of younger patients. TP53 itself showed a higher sensitivity to smoking related C>A mutations in younger LUAD patients. TP53 mutated and TP53 wild type patient groups might represent phenotypes which endure ageing related mutational processes with different strength. LUSC was enriched of defective DNA mismatch repair (MMR) related signatures, in particular the Signature 6 (SI6) in younger and the Signature 26 (SI26) in older patients. Therefore, the two distinct age-related defective DNA MMR signatures SI6 and SI26 might be crucial mutational patterns in LUSC tumorigenesis, which may develop distinct phenotypes. The accumulation of SNPs may not follow distinct mutational patterns but rather an accumulation of mutations in specific pathways. Disruption of Axon Guidance and ECM-extracellular matrix pathways were enriched among the higher mutational rate samples of HNSCC and LUSC. We hypothesize that these pathways might have unknown crucial roles in genome stability maintenance. Further studies with larger numbers of individuals of different ages and diversity of normal tissues are essential to elucidate the intricate relationship between smoking consumption and mutational patterns in relation to intrinsic ageing processes. A better comprehension of tumorigenesis in relation to patient age might be relevant for cancer prevention and age adjusted treatment decisions and should therefore be taken under closer consideration in future studies.Head and Neck Squamous Cell Carcinoma (HNSCC), Lung Squamous Cell Carcinoma (LUSC) und Lung Adenocarcinoma (LUAD) gehören zu den häufigsten Ursachen der weltweiten krebsbedingten Mortalität. Der häufigste gemeinsame Risikofaktor ist hierbei der Rauchkonsum. Durch die Analyse von 203 HNSCC, 480 LUSC und 486 LUAD Proben aus dem „The Cancer Genome Atlas”, untersuchten wir systematisch die Mutationslast sowie Mutationsmuster in Bezug auf das Alter der Patienten. Mehrere Mutationsprozesse scheinen aufgrund der endogenen und exogenen Umgebung, der Lebensgewohnheiten und der physiologischen Alterung gleichzeitig mit verschiedenen dynamischen Veränderungen aufzutreten. Wir fanden einen Anstieg der HNSCC-Mutationsfrequenzrate unabhängig vom Rauchkonsum im Verhältnis zum Patientenalter. Daher könnten mehrere Faktoren zur Anhäufung genetischer Ereignisse bei älteren Menschen beitragen, und die verlängerte Tabakbelastung könnte die altersbedingte SNPs-Belastung erhöhen. Im Gegensatz dazu zeigten LUSC und LUAD eine höhere Mutationsrate bei jüngeren Patienten. TP53-Mutationen bei jüngeren LUAD-Patienten könnten ein entscheidender Faktor sein, der die Empfindlichkeit gegenüber rauchbedingten Mutationen erhöht, was zu einem Ausbruch von somatischen Veränderungen führt. Tatsächlich beeinflussten TP53-Mutationen und das Alter der Patienten signifikant die höhere Mutationsrate jüngerer Patienten. TP53 selbst zeigte eine höhere Empfindlichkeit gegenüber rauchbedingten C> AMutationen bei jüngeren LUAD-Patienten. TP53-mutierte und TP53-Wildtyp-Patientengruppen könnten Phänotypen darstellen, die altersbedingte Mutationsprozesse in unterschiedlichem Maße ertragen. LUSC war angereichert mit defekten DNA Mismatch Repair (MMR) verwandten Signaturen, insbesondere die Signatur 6 (SI6) bei jüngeren und die Signatur 26 (SI26) bei älteren Patienten. Daher könnten die zwei unterschiedlichen altersbedingten defekten DNA-MMRSignaturen SI6 und SI26 entscheidende Mutationsmuster in der LUSC-Tumorgenese sein, die unterschiedliche Phänotypen entwickeln können. Die Akkumulation von SNPs folgt möglicherweise nicht bestimmten Mutationsmustern, sondern eher einer Akkumulation von Mutationen in spezifischen Signalwegen. Eine Unterbrechung der Axon-Führung und der extrazellulären ECM-Matrix-Wege traten bei den Proben mit höheren Mutationsraten von HNSCC und LUSC gehäuft auf. Wir stellen die Hypothese auf, dass diese Wege eine unbekannte und entscheidende Rolle bei der Aufrechterhaltung der Genomstabilität spielen könnten. Weitere Studien mit einer größeren Anzahl von Individuen unterschiedlichen Alters und unterschiedlicher Gewebeverteilung sind essentiell, um den komplizierten Zusammenhang zwischen Rauchkonsum und Mutationsmustern in Bezug auf intrinsische Alterungsprozesse aufzuklären. Ein besseres Verständnis der Tumorgenese in Abhängigkeit vom Patientenalter könnte für die Krebsvorsorge und altersgerechte Behandlungsentscheidungen relevant sein und sollte daher in zukünftigen Studien näher betrachtet werden

Accurate Estimation of Start-Up Pulsating Torque of Direct On Line Synchronous Motors Driving Compressor Trains

Case StudiesIn a compressor train driven by fixed speed synchronous motor (>17MW) was discovered a potential torsional problem on the input shaft of the hydraulic variable speed gear during the start-up phase when only low speed shaft line is engaged. It was due to high motor excitation torque crossing the 1st torsional critical speed during startup causing a very limited numbers of train startups (1400) versus project requirements (5000). Supported by API 617 (8th edition), the motor excitation air-gap torque during startup has been analyzed considering electrical system characteristics that influence the effective voltage drop at motor terminals. A more realistic analysis of the excitation confirmed the correctness of the shaft line design avoiding any redesign and impacts in the projects execution

Infrared refractive indices of liquid crystals

The refractive indices of E7 liquid-crystal mixture were measured at six visible and two infrared (lambda=1.55 and 10.6 mu m) wavelengths at different temperatures, using Abbe and wedged cell refractometer methods, respectively. The experimental data of the visible wavelengths fit the extended Cauchy equations well. Using the extended Cauchy equations, we can extrapolate the refractive indices of E7 to IR. The extrapolated results almost strike through the measured data. Thus, the extended Cauchy equations can be used to link the visible refractive indices to infrared, where the refractive index measurements are more difficult

Importance of Structural Modal Analysis in 2 Poles Induction Motors for LNG Application

Case StudyCase Study 18: High vibrations due to 2X electrical frequency excitation on bearing housings and frame occurred on a 20MW 2-Pole Induction Motors during acceptance tests in manufacturer workshop in stand alone configuration. Modal Analysis results in Factory Acceptance Tests (FAT) configuration were confirmed by Operating Deflection Shape (ODS) and Experimental Modal Analysis (EMA - Hammer test) leading to supports redesign. To mitigate the risk of high vibration in string test bench and customer site, validating also the present motor design, a further Modal Analysis were executed using the experimental data collected during the FAT to drive mode selection

Implementation and Test of a LED-Based Lamp for a Lighthouse

A novel sustainable source was developed for an existing Italian lighthouse, exploiting the light emitting diode (LED) technology and the norms evolution. The research work started with the optical design of the device, while this work concerns the realization, installation, and test of the new LED lamp. The lamp recombines multiple separated LEDs, realizing a quasipunctual localized source. After installation in the lighthouse, specific photometric tests verified that the proposed power-saving source satisfied the illumination requirements of the marine signaling norms. The advantages of the LED-based lamp are reduced energy consumption, enhanced efficiency, longer life, decreased faults, slower aging, and lower maintenance costs. The obtained LED signalling device is more durable and reliable. In the future the application of these power-saving long-life sources could be extended to other maritime signaling devices or to other traffic signs

Accurate Estimation of Start-Up Pulsating Torque of Direct On Line Synchronous Motors Driving Compressor Trains

Case StudiesIn a compressor train driven by fixed speed synchronous motor (>17MW) was discovered a potential torsional problem on the input shaft of the hydraulic variable speed gear during the start-up phase when only low speed shaft line is engaged. It was due to high motor excitation torque crossing the 1st torsional critical speed during startup causing a very limited numbers of train startups (1400) versus project requirements (5000). Supported by API 617 (8th edition), the motor excitation air-gap torque during startup has been analyzed considering electrical system characteristics that influence the effective voltage drop at motor terminals. A more realistic analysis of the excitation confirmed the correctness of the shaft line design avoiding any redesign and impacts in the projects execution

Archeometrical Analysis for the Characterization of Mortars from Ostia Antica

AbstractThe aim of the study is to provide, through the characterization of the mortar samples and the relative raw materials, useful information in order to define the stages of construction, the workers technological and archaeological knowledge. The study is an interdisciplinary approach carried out by different analysis techniques in order to define the mineral-petrographic composition and highlight the differences among the various samples. Mortars are present in all the walls, except dry ones, as a bedding material and as a coating. The mortars may be regarded as markers for excellence, because they must be prepared at the time of their use, during the construction of the masonry, and cannot be re-used after their hardening and socket. Furthermore, the production of mortars in the past depended on the availability of raw materials in situ thus establishing a strong and direct correlation between the origin and use.The chemical and petrographic study of the subtle differences and composition of the mortar makes it possible to use this material as an excellent timeline if the supply of building materials varies over time. Mortars, for these reasons, play two key roles in archaeological survey: an absolutely priority for the correct determination of the contours of Stratigraphic Units; the role of the typological class very representative and very useful for making comparisons between different parts of the building and connecting between them the activities of the individual site