Novel spectral kurtosis technology for adaptive vibration condition monitoring of multi-stage gearboxes

In this paper, the novel wavelet spectral kurtosis (WSK) technique is applied for the early diagnosis of gear tooth faults. Two variants of the wavelet spectral kurtosis technique, called variable resolution WSK and constant resolution WSK, are considered for the diagnosis of pitting gear faults. The gear residual signal, obtained by filtering the gear mesh frequencies, is used as the input to the SK algorithm. The advantages of using the wavelet-based SK techniques when compared to classical Fourier transform (FT)-based SK is confirmed by estimating the toothwise Fisher's criterion of diagnostic features. The final diagnosis decision is made by a three-stage decision-making technique based on the weighted majority rule. The probability of the correct diagnosis is estimated for each SK technique for comparison. An experimental study is presented in detail to test the performance of the wavelet spectral kurtosis techniques and the decision-making technique

Neural Substrates of Chronic Pain in the Thalamocortical Circuit

Chronic pain (CP), a pathological condition with a large repertory of signs and symptoms, has no recognizable neural functional common hallmark shared by its diverse expressions. The aim of the present research was to identify potential dynamic markers shared in CP models, by using simultaneous electrophysiological extracellular recordings from the rat ventrobasal thalamus and the primary somatosensory cortex. We have been able to extract a neural signature attributable solely to CP, independent from of the originating conditions. This study showed disrupted functional connectivity and increased redundancy in firing patterns in CP models versus controls, and interpreted these signs as a neural signature of CP. In a clinical perspective, we envisage CP as disconnection syndrome and hypothesize potential novel therapeutic appraisal

Resonances and nonlinear vibrations of circular cylindrical shells, effects of thermal gradients

In this paper, the results of an experimental campaign focused on the vibrations of shells are presented. More specifically, the goal is to investigate the effect of thermal gradients across the shell thickness on the nonlinear dynamics. The shell is made of polymeric material and an aluminum mass is clamped on one end of the shell; the other shell end is clamped to an electrodynamic shaker, which provides a base harmonic excitation. Tests are performed in a controlled environment where a thermal gradient on the shell thickness is generated by means of a climatic chamber and an internal cartridge heater. Different temperature gradients and base excitation levels have been considered. The nonlinear dynamic scenario is analyzed through amplitude–frequency diagrams, bifurcation diagrams, waterfall diagrams, time histories, Fourier spectra, phase portraits, and Poincaré maps. Results show a strong effect of the temperature on the dynamic response of the shell: subharmonic, quasi-periodic, and chaotic vibrations take place as well as large amplitude vibrations, high sound levels are detected

po 298 myc favours the onset of tumour initiating cells by inducing epigenetic reprogramming of mammary epithelial cells towards a stem cell like state

Introduction Breast cancer consists of highly heterogenous tumours whose cell of origin resulted difficult to be defined. Recent findings highlighted the possibility that tumor-initiating cells (TICs) may arise from dedifferentiation of lineage-committed cells, by reactivation of multipotency in response to oncogenic insults. MYC is the most frequently amplified oncogene in breast cancer and the activation of MYC pathway has been associated with the basal-like subtype, which is characterised by poor survival and lack of a specific therapeutic strategy. Although MYC has been considered a driver oncogene in breast cancer, its mechanism of action in tumour initiation has been poorly addressed. Material and methods To evaluate the role of MYC in perturbing cell identity of somatic cells, we transduced hTERT-immortalised human mammary epithelial cells (IMEC) with a retroviral vector expressing low levels of the exogenous c-Myc. The effect of MYC overexpression was evaluated by performing morphological analysis and gene expression profiling. To verify whether MYC overexpression could enrich for cells with functional stem cell-like properties, we performed mammospheres assay. ChIP-seq analyses were performed to profile chromatin modifications and MYC binding in IMEC WT, -MYC and mammospheres. To determine whether MYC-reprogrammed IMEC were enriched for TICs, we performed in vivo injection in NOD/SCID mice and assessed long-term tumorigenic potential by performing serial transplantation assay. To assess the clinical relevance of our findings, we investigated the expression of MYC-dependent oncogenic signature in a database of breast cancer patients. Results and discussions Overexpression of MYC induces transcriptional repression of lineage-specifying transcription factors, causing decommissioning of luminal-specific enhancers. Of note, MYC-driven dedifferentiation supports the onset of a basal/stem cell-like state by inducing the activation of de novo enhancers, which drive the transcriptional activation of oncogenic pathways. MYC-driven epigenetic reprogramming favours the formation and maintenance of TICs endowed with metastatic capacity. Moreover, oncogenic pathways activated by MYC-modulated enhancers are associated with basal-like breast cancer in patients with a poor prognosis. Conclusion MYC-driven tumour initiation relies on a cell reprogramming process, which is mediated by activation of MYC-dependent oncogenic enhancers, thus establishing a therapeutic rational for treating basal-like breast cancers

Poly-acetylated chromatin signatures are preferred epitopes for site-specific histone H4 acetyl antibodies

Antibodies specific for histone post-translational modifications (PTMs) have been central to our understanding of chromatin biology. Here, we describe an unexpected and novel property of histone H4 site-specific acetyl antibodies in that they prefer poly-acetylated histone substrates. By all current criteria, these antibodies have passed specificity standards. However, we find these site-specific histone antibodies preferentially recognize chromatin signatures containing two or more adjacent acetylated lysines. Significantly, we find that the poly-acetylated epitopes these antibodies prefer are evolutionarily conserved and are present at levels that compete for these antibodies over the intended individual acetylation sites. This alarming property of acetyl-specific antibodies has far-reaching implications for data interpretation and may present a challenge for the future study of acetylated histone and non-histone proteins

Genome-wide H4 K16 acetylation by SAS-I is deposited independently of transcription and histone exchange

The MYST HAT Sas2 is part of the SAS-I complex that acetylates histone H4 lysine 16 (H4 K16Ac) and blocks the propagation of heterochromatin at the telomeres of Saccharomyces cerevisiae. In this study, we investigated Sas2-mediated H4 K16Ac on a genome-wide scale. Interestingly, H4 K16Ac loss in sas2Δ cells outside of the telomeric regions showed a distinctive pattern in that there was a pronounced decrease of H4 K16Ac within the majority of open reading frames (ORFs), but little change in intergenic regions. Furthermore, regions of low histone H3 exchange and low H3 K56 acetylation showed the most pronounced loss of H4 K16Ac in sas2Δ, indicating that Sas2 deposited this modification on chromatin independently of histone exchange. In agreement with the effect of Sas2 within ORFs, sas2Δ caused resistance to 6-azauracil, indicating a positive effect on transcription elongation in the absence of H4 K16Ac. In summary, our data suggest that Sas2-dependent H4 K16Ac is deposited into chromatin independently of transcription and histone exchange, and that it has an inhibitory effect on the ability of PolII to travel through the body of the gene