Dynamic analysis of modified composite helicopter blade

U ovom radu izvršena je modalna analiza modifikovane lopatice helikoptera 'Gazela'. Modifikovana lopatica je kompletno kompozitna sa saćastom ispunom. Prikazan je metod određivanja modova oscilovanja i sopstvenih frekvencija. Modifikovana lopatica sastoji se od saćaste ispune, ramenjače od 3D usmerenog kompozita i tankih karbonskih ploča kao oplate. Da bi se odredila matrica krutosti ispune korišćen je metod ekvivalentnih masa. U cilju nalaženja optimalnog metoda za određivanje sopstvenih frekvencija ispitano je nekoliko poznatih metoda. Metod Lancosa pokazao je najtačnije rezultate kroz umereno procesorsko vreme kada je u pitanju određivanje sopstvenih frekvencija i modova oscilovanja kod struktura od kompozitnih materijala sa saćastim ispunama. Ovom metodom izračunata su prva četiri moda oscilovanja modifikovane kompozitne lopatice, i prikazani su rezultati modova oscilovanja i deformacione energije lopatice.In the present study, modal analysis has been performed on modified Gazelle helicopter blade. The construction of the blade is fully composite with the honeycomb core. The approach to determining structure mode shapes and natural frequencies is presented. Modified blade consists of core material, 3D unidirectional composite spar and thin carbon composite facesheets as blade skin. To determine the stiffness of the honeycomb core, the equivalent mass approach was used. Several methods of eigenvalue extraction have been investigated in order to find optimal method which can be used in dynamic analysis of composite structures containing honeycomb cores. Among all extraction methods investigated, it was found that combined Lanczos method is most effective in terms of accuracy and CPU time for eigenvalue extraction in composite structures with honeycomb core having large number of degrees of freedom. Strain energies for first four mode shapes of modified helicopter blade have been calculated using numerical approach and results are presented

Dynamic analysis of modified composite helicopter blade

U ovom radu izvršena je modalna analiza modifikovane lopatice helikoptera 'Gazela'. Modifikovana lopatica je kompletno kompozitna sa saćastom ispunom. Prikazan je metod određivanja modova oscilovanja i sopstvenih frekvencija. Modifikovana lopatica sastoji se od saćaste ispune, ramenjače od 3D usmerenog kompozita i tankih karbonskih ploča kao oplate. Da bi se odredila matrica krutosti ispune korišćen je metod ekvivalentnih masa. U cilju nalaženja optimalnog metoda za određivanje sopstvenih frekvencija ispitano je nekoliko poznatih metoda. Metod Lancosa pokazao je najtačnije rezultate kroz umereno procesorsko vreme kada je u pitanju određivanje sopstvenih frekvencija i modova oscilovanja kod struktura od kompozitnih materijala sa saćastim ispunama. Ovom metodom izračunata su prva četiri moda oscilovanja modifikovane kompozitne lopatice, i prikazani su rezultati modova oscilovanja i deformacione energije lopatice.In the present study, modal analysis has been performed on modified Gazelle helicopter blade. The construction of the blade is fully composite with the honeycomb core. The approach to determining structure mode shapes and natural frequencies is presented. Modified blade consists of core material, 3D unidirectional composite spar and thin carbon composite facesheets as blade skin. To determine the stiffness of the honeycomb core, the equivalent mass approach was used. Several methods of eigenvalue extraction have been investigated in order to find optimal method which can be used in dynamic analysis of composite structures containing honeycomb cores. Among all extraction methods investigated, it was found that combined Lanczos method is most effective in terms of accuracy and CPU time for eigenvalue extraction in composite structures with honeycomb core having large number of degrees of freedom. Strain energies for first four mode shapes of modified helicopter blade have been calculated using numerical approach and results are presented

The Role of Metformin in the Management of NAFLD

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder worldwide. Its prevalence ranges 10–24% in the general population, reaching 60–95% and 28–55% in obese and diabetic patients, respectively. Although the etiology of NAFLD is still unclear, several lines of evidences have indicated a pathogenetic role of insulin resistance in this disorder. This concept has stimulated several clinical studies where antidiabetic drugs, such as insulin sensitizers including metformin, have been evaluated in insulin-resistant, NAFLD patients. These studies indicate that metformin might be of benefit in the treatment of NAFLD, also in nondiabetic patients, when associated to hypocaloric diet and weight control. However, the heterogeneity of these studies still prevents us from reaching firm conclusions about treatment guidelines. Moreover, metformin could have beneficial tissue-specific effects in NAFLD patients irrespective of its effects as insulin sensitizer

Transcriptome and phenotypic analysis reveals Gata3-dependent signalling pathways in murine hair follicles

Abstract The transcription factor Gata3 is crucially involved in epidermis and hair follicle differentiation. Yet, little is known about how Gata3 co-ordinates stem cell lineage determination in skin, what pathways are involved and how Gata3 differentially regulates distinct cell populations within the hair follicle. Here, we describe a conditional Gata3-/- mouse (K14-Gata3-/-) in which Gata3 is specifically deleted in epidermis and hair follicles. K14-Gata3-/- mice show aberrant postnatal growth and development, delayed hair growth and maintenance, abnormal hair follicle organization and irregular pigmentation. After the first hair cycle, the germinative layer surrounding the dermal papilla was not restored; instead, proliferation was pronounced in basal epidermal cells. Transcriptome analysis of laser-dissected K14-Gata3-/- hair follicles revealed mitosis, epithelial differentiation and the Notch, Wnt and BMP signaling pathways to be significantly overrepresented. Elucidation of these pathways at the RNA and protein levels and physiologic endpoints suggests that Gata3 integrates diverse signaling networks to regulate the balance between hair follicle and epidermal cell fates

Transcriptional impairment of β-catenin/E-cadherin complex is not associated with β-catenin mutations in colorectal carcinomas

We report the absence of β-catenin mutations in 63 sporadic colorectal carcinomas (SCRCs) with demonstrated decreased β-catenin and E-cadherin mRNA expression and E-cadherin protein expression in a subset of carcinomas examined, suggesting that β-catenin mutations are an extremely rare phenomenon in SCRCs and are not responsible for the transcriptional impairment of the β-catenin/E-cadherin adhesion complex observed in these tumours

The splicing factor XAB2 interacts with ERCC1-XPF and XPG for R-loop processing

RNA splicing, transcription and the DNA damage response are intriguingly linked in mammals but the underlying mechanisms remain poorly understood. Using an in vivo biotinylation tagging approach in mice, we show that the splicing factor XAB2 interacts with the core spliceosome and that it binds to spliceosomal U4 and U6 snRNAs and pre-mRNAs in developing livers. XAB2 depletion leads to aberrant intron retention, R-loop formation and DNA damage in cells. Studies in illudin S-treated cells and Csb(m/m) developing livers reveal that transcription-blocking DNA lesions trigger the release of XAB2 from all RNA targets tested. Immunoprecipitation studies reveal that XAB2 interacts with ERCC1-XPF and XPG endonucleases outside nucleotide excision repair and that the trimeric protein complex binds RNA:DNA hybrids under conditions that favor the formation of R-loops. Thus, XAB2 functionally links the spliceosomal response to DNA damage with R-loop processing with important ramifications for transcription-coupled DNA repair disorders

R-loops trigger the release of cytoplasmic ssDNAs leading to chronic inflammation upon DNA damage

How DNA damage leads to chronic inflammation and tissue degeneration with aging remains to be fully resolved. Here, we show that DNA damage leads to cellular senescence, fibrosis, loss-of-tissue architecture, and chronic pancreatitis in mice with an inborn defect in the excision repair cross complementation group 1 (Ercc1) gene. We find that DNA damage-driven R-loops causally contribute to the active release and buildup of single-stranded DNAs (ssDNAs) in the cytoplasm of cells triggering a viral-like immune response in progeroid and naturally aged pancreata. To reduce the proinflammatory load, we developed an extracellular vesicle (EV)-based strategy to deliver recombinant S1 or ribonuclease H nucleases in inflamed Ercc1(−/−) pancreatic cells. Treatment of Ercc1(−/−) animals with the EV-delivered nuclease cargo eliminates DNA damage-induced R-loops and cytoplasmic ssDNAs alleviating chronic inflammation. Thus, DNA damage-driven ssDNAs causally contribute to tissue degeneration, Ercc1(−/−) paving the way for novel rationalized intervention strategies against age-related chronic inflammation

Fluorescent probes for the analysis of DNA strand scission in base excision repair

We have developed fluorescent probes for the detection of strand scission in the excision repair of oxidatively damaged bases. They were hairpin-shaped oligonucleotides, each containing an isomer of thymine glycol or 5,6-dihydrothymine as a damaged base in the center, with a fluorophore and a quencher at the 5′- and 3′-ends, respectively. Fluorescence was detected when the phosphodiester linkage at the damage site was cleaved by the enzyme, because the short fragment bearing the fluorophore could not remain in a duplex form hybridized to the rest of the molecule at the incubation temperature. The substrate specificities of Escherichia coli endonuclease III and its human homolog, NTH1, determined by using these probes agreed with those determined previously by gel electrophoresis using 32P-labeled substrates. Kinetic parameters have also been determined by this method. Since different fluorophores were attached to the oligonucleotides containing each lesion, reactions with two types of substrates were analyzed separately in a single tube, by changing the excitation and detection wavelengths. These probes were degraded during an incubation with a cell extract. Therefore, phosphorothioate linkages were incorporated to protect the probes from nonspecific nucleases, and the base excision repair activity was successfully detected in HeLa cells