Influence of SiO2 micro-particles onto microstructure, mechanical properties and wear resistance of uhmwpe based composite under dry sliding friction

Operation is demonstrated of a field-effect transistor made of transparant oxidic thin films, showing an intrinsic memory function due to the usage of a ferroelectric insulator. The device consists of a high mobility Sb-doped n-type SnO2 semiconductor layer, PbZr0.2Ti0.8O3 as a ferroelectric insulator, and SrRuO3 as a gate electrode, each layer prepared by pulsed laser deposition. The hysteresis behavior of the channel conductance is studied. Using gate voltage pulses of 100 µs duration and a pulse height of ±3 V, a change of a factor of two in the remnant conductance is achieved. The dependence of the conductance on the polarity of the gate pulse proves that the memory effect is driven by the ferroelectric polarization. The influence of charge trapping is also observed and discussed. © 1996 American Institute of Physics

A microRNA prognostic signature in patients with diffuse intrinsic pontine gliomas through non-invasive liquid biopsy

Diffuse midline gliomas (DMGs) originate in the thalamus, brainstem, cerebellum and spine. This entity includes tumors that infiltrate the pons, called diffuse intrinsic pontine gliomas (DIPGs), with a rapid onset and devastating neurological symptoms. Since surgical removal in DIPGs is not feasible, the purpose of this study was to profile circulating miRNA expression in DIPG patients in an effort to identify a non-invasive prognostic signature with clinical impact. Using a high-throughput platform, miRNA expression was profiled in serum samples collected at the time of MRI diagnosis and prior to radiation and/or systemic therapy from 47 patients enrolled in clinical studies, combining nimotuzumab and vinorelbine with concomitant radiation. With progression-free survival as the primary endpoint, a semi-supervised learning approach was used to identify a signature that was also tested taking overall survival as the clinical endpoint. A signature comprising 13 circulating miRNAs was identified in the training set (n = 23) as being able to stratify patients by risk of disease progression (log-rank p = 0.00014; HR = 7.99, 95% CI 2.38–26.87). When challenged in a separate validation set (n = 24), it confirmed its ability to predict progression (log-rank p = 0.00026; HR = 5.51, 95% CI 2.03–14.9). The value of our signature was also confirmed when overall survival was considered (log-rank p = 0.0021, HR = 4.12, 95% CI 1.57–10.8). We have identified and validated a prognostic marker based on the expression of 13 circulating miRNAs that can shed light on a patient’s risk of progression. This is the first demonstration of the usefulness of nucleic acids circulating in the blood as powerful, easy-to-assay molecular markers of disease status in DIPG. This study provides Class II evidence that a signature based on 13 circulating miRNAs is associated with the risk of disease progression

Tumor biomarkers for the prediction of distant metastasis in head and neck squamous cell carcinoma

19openopenSalvatore Alfieri Andrea Carenzo, Francesca Platini, Mara S Serafini, Federica Perrone, Donata Galbiati, Andrea P Sponghini, Roberta Depenni, Andrea Vingiani, Pasquale Quattrone, Edoardo Marchesi, Maria F Iannó, Arianna Micali, Elisa Mancinelli, Ester Orlandi, Sara Marceglia, Laura D Locati, Lisa Licitra , Paolo Bossi, Loris De CeccoAlfieri Andrea Carenzo, Salvatore; Platini, Francesca; S Serafini, Mara; Perrone, Federica; Galbiati, Donata; P Sponghini, Andrea; Depenni, Roberta; Vingiani, Andrea; Quattrone, Pasquale; Marchesi, Edoardo; F Iannó, Maria; Micali, Arianna; Mancinelli, Elisa; Orlandi, Ester; Marceglia, Sara; D Locati, Laura; Licitra, Lisa; Bossi, Paolo; De Cecco, Lori

Case report: biallelic DNMT3A mutations in acute myeloid leukemia

DNMT3A gene mutations, detected in 20-25% of de novo acute myeloid leukemia (AML) patients, are typically heterozygous. Biallelic variants are uncommon, affecting ~3% of cases and identifying a worse prognosis. Indeed, two concomitant DNMT3A mutations were recently associated with shorter event-free survival and overall survival in AML. We present an AML case bearing an unusual DNMT3A molecular status, strongly affecting its function and strangely impacting the global genomic methylation profile. A 56-year-old Caucasian male with a diagnosis of AML not otherwise specified (NOS) presented a complex DNMT3A molecular profile consisting of four different somatic variants mapping on different alleles (in trans). 3D modelling analysis predicted the effect of the DNMT3A mutational status, showing that all the investigated mutations decreased or abolished DNMT3A activity. Although unexpected, DNMT3A’s severe loss of function resulted in a global genomic hypermethylation in genes generally involved in cell differentiation. The mechanisms through which DNMT3A contributes to AML remain elusive. We present a unique AML case bearing multiple biallelic DNMT3A variants abolishing its activity and resulting in an unexpected global hypermethylation. The unusual DNMT3A behavior described requires a reflection on its role in AML development and persistence, highlighting the heterogeneity of its deregulation