Experimental and numerical studies of inclined cables: free and parametrically-forced vibrations

Because of few experimental studies in the inclined cable literature, this paper is aimed at experimental modelling and investigating the linear free and nonlinear forced vibrations of sagged inclined cables, by discussing the relevant outcomes in the background of theoretical and numerical achievements. Attention is paid to the identification of cable hybrid modes due to system asymmetry, which gives rise to an avoidance phenomenon in the natural frequency spectrum, and to the investigation of some typical 3-D nonlinear dynamics involving the simultaneous parametric/external excitation due to a harmonically time-varying support movement. Large-amplitude out-of-plane/in-plane multi-modal interactions due to non-planar/planar internal resonances are experimentally observed and complemented by space-time numerical simulation of the associated, geometrically nonlinear, partial-differential equations of parametrically-forced cable motion. Overall, the experimental and numerical results highlight the fundamental linear/nonlinear dynamic characteristics of inclined cables, and the crucial role played by the asymmetry induced by cable inclination, in addition to the significant effects of cable sag and dynamic extensibility

Experimental and Analytical Investigation into the Effect of Ballasted Track on the Dynamic Response of Railway Bridges under Moving Loads

Ballasted tracks are among the most widespread railway track typologies. The ballast possesses multiple functions. Among them, it significantly affects the dynamic interaction between a rail bridge and a moving load in terms of damping and load distribution. These effects entail accurate modeling of the track-ballast-bridge interaction. The paper presents a finite-difference formulation of the governing equations of the track and the bridge, modeled as Euler-Bernoulli (EB) beams, and coupled by a distributed layer of springs representing the ballast. The two equations are solved under a moving load excitation using a Runge-Kutta family algorithm and the finite-difference method for the temporal and spatial discretization, respectively. The authors validated the mathematical model against the displacement response of a rail bridge with a ballasted substructure. In a first step, the modal parameters of the bridge, obtained from ambient vibration measurements, are used to estimate the bending stiffness of an equivalent EB beam representative of the tested bridge. In a second step, the authors estimated the coupling effect of the ballast by assessing the model sensitivity to the modeling parameters and optimizing the agreement with the experimental data. Comparing the bridge's experimental displacement responses highlights the ballast's significant effect on the load distribution and damping. The considerable difference between the damping estimated from output-only identification and that determined from the displacement response under moving load proves the dominant role of the ballast in adsorbing the vibrations transmitted to the bridge under the train passage and the different damping sources under high-amplitude excitation. The authors discuss the tradeoff between model accuracy and computational effort for a reliable estimation of ballasted tracks response under moving loads

NTRK3 overexpression in undifferentiated sarcomas with YWHAE and BCOR genetic alterations

The BCOR family of tumors includes a number of undifferentiated sarcomas, occurring in various age groups and anatomic sites, characterized by a spindle and round cell phenotype and diffuse immunoreactivity for BCOR. Prior RNA sequencing data revealed that NTRK3 was a top-upregulated gene in BCOR-CCNB3 sarcomas. In this study, we investigate a large cohort of tumors harboring BCOR/YWHAE genetic alterations for NTRK3 upregulation at both the mRNA and protein levels, compared with other sarcoma types. Pan-Trk immunohistochemistry was assessed for intensity and extent. A correlation between NTRK3 expression and the type of BCOR alteration and BCOR immunoreactivity was also performed. Most soft tissue undifferentiated round cell sarcomas with YWHAE or BCOR rearrangements or BCOR internal tandem duplications (ITD) showed NTRK3, but not NTRK1 or NTRK2, upregulation by RNA sequencing data analysis. Cytoplasmic pan-Trk immunoreactivity was also observed in most soft tissue round cell sarcomas with YWHAE rearrangements (100%), BCOR ITD (80%), and BCOR-CCNB3 fusions (67%), as well as clear cell sarcomas of kidney (75%), another BCOR family tumor, and ossifying fibromyxoid tumors with ZC3H7B-BCOR fusion (100%), with variable staining intensity and extent. Pan-Trk staining was also seen in solitary fibrous tumors (100%) and less frequently in synovial sarcoma and Ewing sarcoma, but rarely in other sarcomas tested. Tumors harboring rare fusion variants of BCOR, such as BCOR-CHD9, a novel fusion identified by targeted RNA sequencing, and KMT2D-BCOR, were also positive for pan-Trk staining and NTRK3 overexpression. In conclusion, NTRK3 upregulation resulting in pan-Trk overexpression is common in the BCOR family of tumors as well as in subsets of BCOR-expressing sarcomas through alternative mechanisms. The therapeutic implication of this finding awaits further investigation

BCOR Overexpression Is a Highly Sensitive Marker in Round Cell Sarcomas With BCOR Genetic Abnormalities

open10With the advent of next-generation sequencing, an increasing number of novel gene fusions and other abnormalities have emerged recently in the spectrum of EWSR1-negative small blue round cell tumors (SBRCTs). In this regard, a subset of SBRCTs harboring either BCOR gene fusions (BCOR-CCNB3, BCOR-MAML3), BCOR internal tandem duplications (ITD), or YWHAE-NUTM2B share a transcriptional signature including high BCOR mRNA expression, as well as similar histologic features. Furthermore, other tumors such as clear cell sarcoma of kidney (CCSK) and primitive myxoid mesenchymal tumor of infancy also demonstrate BCOR ITDs and high BCOR gene expression. The molecular diagnosis of these various BCOR genetic alterations requires an elaborate methodology including custom BAC fluorescence in situ hybridization (FISH) probes and reverse transcription polymerase chain reaction assays. As these tumors show high level of BCOR overexpression regardless of the genetic mechanism involved, either conventional gene fusion or ITD, we sought to investigate the performance of an anti-BCOR monoclonal antibody clone C-10 (sc-514576) as an immunohistochemical marker for sarcomas with BCOR gene abnormalities. Thus we assessed the BCOR expression in a pathologically and genetically well-characterized cohort of 25 SBRCTs, spanning various BCOR-related fusions and ITDs and YWHAE-NUTM2B fusion. In addition, we included related pathologic entities such as 8 CCSKs and other sarcomas with BCOR gene fusions. As a control group we included 20 SBRCTs with various (non-BCOR) genetic abnormalities, 10 fusion-negative SBRCTs, 74 synovial sarcomas, 29 rhabdomyosarcomas, and other sarcoma types. In addition, we evaluated the same study group for SATB2 immunoreactivity, as these tumors also showed SATB2 mRNA upregulation. All SBRCTs with BCOR-MAML3 and BCOR-CCNB3 fusions, as well as most with BCOR ITD (93%), and all CCSKs showed strong and diffuse nuclear BCOR immunoreactivity. Furthermore, all SBRCTs with YWHAE-NUTM2B also were positive. SATB2 stain was also positive in tumors with YWHAE-NUTM2B, BCOR-MAML3, BCOR ITD (75%), BCOR-CCNB3 (71%), and a subset of CCSKs (33%). In conclusion, BCOR immunohistochemical stain is a highly sensitive marker for SBRCTs and CCSKs with BCOR abnormalities and YWHAE-rearrangements and can be used as a useful diagnostic marker in these various molecular subsets. SATB2 immunoreactivity is also present in the majority of this group of tumors.openKao, Yc; Sung, Ys; Zhang, L; Jungbluth, Aa; Huang, Sc; Argani, P; Agaram, Np; Zin, A; Alaggio, R; Antonescu, CrKao, Yc; Sung, Ys; Zhang, L; Jungbluth, Aa; Huang, Sc; Argani, P; Agaram, Np; Zin, A; Alaggio, Rita; Antonescu, C

Undifferentiated round cell sarcoma with BCOR internal tandem duplications (ITD) or YWHAE fusions:a clinicopathologic and molecular study

Until recently, undifferentiated round cell sarcomas (URCS) in infants have been considered a wastebasket diagnosis, composed of various pathologic entities and lacking consistent genetic alterations. The recent identification of recurrent BCOR internal tandem duplications (ITD) and less common alternative YWHAE\u2013NUTM2B/E fusions in half of infantile URCS and the majority of so-called primitive myxoid mesenchymal tumors of infancy (PMMTI) suggests a common pathogenesis with clear cell sarcoma of the kidney which also harbors the same genetic alterations. These tumors also share a similar morphology and immunoprofile, including positivity for BCOR, cyclin D1, and SATB2. In this study, we investigate the largest cohort to date of genetically confirmed URCS and PMMTI with BCOR ITD or YWHAE fusions to better define their morphologic spectrum and clinical behavior. Twenty-eight cases harbored BCOR ITD and five YWHAE fusions, occurring in 29 infants and 4 children, 19 males and 14 females. Microscopically, 20 were classified as URCS and 13 as PMMTI. Follow-up was available in 25 patients, with 14 (56%) succumbing to their diseases at a mean duration of 18-months follow-up (range: 2\u201362). Six patients remained with no evidence of disease at a mean follow-up of 63 months (range: 4\u2013192), four patients were still alive with disease (mean follow-up: 46 months, range: 4\u2013120), and one died of other causes. Local recurrence and distant metastasis were each observed in 11/25 (44%) of the patients. The overall survival was 42% at 3 years and 34% at 5 years (median survival: 26 months). There was no statistically significant survival difference between cases diagnosed as URCS and PMMTI and between those with BCOR ITD and YWHAE fusions