Devices based on 2D materials for on-chip amplification of ionization charges

Pixels detectors are widely used ionizing radiation detection devices in high-energy physics (HEP)experiments. Segmented detectors have been employed for many years due to the need to simul-taneously track the thousands of particles emerging from modern colliders. For more preciseand accurate measurements one would like to have faster, less noisy and smaller pixels, but cur-rent technology imposes several limits on these characteristics. The aim of this work is to ex-plore the possible applications of bi-dimensional materials such as Graphene or transition metaldichalcogenide monolayers (TMDs) to address these problems. In particular, one wants to de-termine whether nano-electronic devices based on 2D materials could be used to obtain built-inpre-amplification of the pixel signal, thus achieving better detection performance. The workingprinciple is the field-effect modulation of the channel conductivity in a 2D material-based tran-sistor, due to the presence of ionization charges in a silicon absorber. Several architectures aretested, and a final device of choice is presented, with a sketch of a realistic readout system andits noise figure. The conductance modulation due to incoming particles is found to be more than30%, resulting in a strong current signal, which leads to very favourable signal-to-noise ratios (SNR)

Energy-Aware Weight Assignment Framework for Circuit Oriented GMPLS Networks

A branch of green networking research is consolidating. It aims at routing traffic with the goal of reducing the network energy consumption. It is usually referred to as Energy- Aware Routing. Previous works in this branch only focused on pure IP networks, e.g., assuming an Open Shortest Path First (OSPF) control plane, and best effort packet forwarding on the data plane. In this work, we consider instead Generalized Multi-Protocol Label Switching (GMPLS) backbone networks, where optical technologies allow to design "circuit switching" network management policies with strict bandwidth reservation policies. We define a simple and generic framework which generates a family of routing algorithms, based on an energy-aware weight assignment. In particular, routing weights are functions of both the energy consumption and the actual load of network devices. Using such weights, a simple minimum-cost routing allows finding the current least expensive circuit, minimising the additional energy cost. Results obtained on realistic case studies show that our weight assignment policy favours a consistent reduction of the network power consumption, without significantly affecting the network performance. Furthermore, the framework allows to trade energy efficiently and network performance, a desirable property at which ISPs are looking for. Simple and robust parameter settings allow reaching a win-win situation, with excellent performance in terms of both energy efficiency and network resource utilization

MOLECULAR IDENTIFICATION AND GENOTYPING OF CIAUSCOLO AUTOCHTHONOUS MICROFLORA: PRELIMINARY STUDY

The present study reports the results of a preliminary characterization of the bacterial population of Ciauscolo, a typical Italian fermented sausage, traditionally manufactured in Marche region. The bacterial community involved in Ciauscolo fermentation was investigated using both molecular and culturebased methods. The estimation of genotypic intra-species variation of the autochthonous bacteria isolated was also evaluated by using randomly amplified polymorphic DNA (RAPD) analysis and unweighted pairgroup method with arithmetic averages (UPGMA) cluster analysis. Our findings revealed an high diversity of the autochthonous bacterial population investigated, both at species and strain level

OVOL2 impairs RHO GTPase signaling to restrain mitosis and aggressiveness of Anaplastic Thyroid Cancer

Background: Anaplastic Thyroid Cancer (ATC) is an undifferentiated and aggressive tumor that often originates from well-Differentiated Thyroid Carcinoma (DTC) through a trans-differentiation process. Epithelial-to-Mesenchymal Transition (EMT) is recognized as one of the major players of this process. OVOL2 is a transcription factor (TF) that promotes epithelial differentiation and restrains EMT during embryonic development. OVOL2 loss in some types of cancers is linked to aggressiveness and poor prognosis. Here, we aim to clarify the unexplored role of OVOL2 in ATC. Methods: Gene expression analysis in thyroid cancer patients and cell lines showed that OVOL2 is mainly associated with epithelial features and its expression is deeply impaired in ATC. To assess OVOL2 function, we established an OVOL2-overexpression model in ATC cell lines and evaluated its effects by analyzing gene expression, proliferation, invasion and migration abilities, cell cycle, specific protein localization through immunofluorescence staining. RNA-seq profiling showed that OVOL2 controls a complex network of genes converging on cell cycle and mitosis regulation and Chromatin Immunoprecipitation identified new OVOL2 target genes. Results: Coherently with its reported function, OVOL2 re-expression restrained EMT and aggressiveness in ATC cells. Unexpectedly, we observed that it caused G2/M block, a consequent reduction in cell proliferation and an increase in cell death. This phenotype was associated to generalized abnormalities in the mitotic spindle structure and cytoskeletal organization. By RNA-seq experiments, we showed that many pathways related to cytoskeleton and migration, cell cycle and mitosis are profoundly affected by OVOL2 expression, in particular the RHO-GTPase pathway resulted as the most interesting. We demonstrated that RHO GTPase pathway is the central hub of OVOL2-mediated program in ATC and that OVOL2 transcriptionally inhibits RhoU and RhoJ. Silencing of RhoU recapitulated the OVOL2-driven phenotype pointing to this protein as a crucial target of OVOL2 in ATC. Conclusions: Collectively, these data describe the role of OVOL2 in ATC and uncover a novel function of this TF in inhibiting the RHO GTPase pathway interlacing its effects on EMT, cytoskeleton dynamics and mitosis

Dental enamel, fluorosis and amoxicillin

Introduction: Amoxicillin is one of the most used antibiotics among pediatric patients for the treatment of upper respiratory tract infections and specially for acute otitis media (AOM), a common diseases of infants and childhood. It has been speculated that the use of amoxicillin during early childhood could be associated with dental enamel fluorosis, also described in literature with the term Molar Incisor Hypomineralization (MIH), because they are generally situated in one or more 1st permanent molars and less frequently in the incisors. The effect of Amoxicillin seems to be independent of other risk factors such as fluoride intake, prematurity, hypoxia, hypocalcaemia, exposure to dioxins, chikenpox, otitis media, high fever and could have a significant impact on oral health for the wide use of this drug in that period of life. Objective: The aim of this work was to review the current literature about the association between amoxicillin and fluorosis. Methods and Results: A literature survey was done by applying the Medline database (Entrez PubMed); the Cochrane Library database of the Cochrane Collaboration (CENTRAL). The databases were searched using the following strategy and keywords: amoxicillin* AND (dental fluorosis* OR dental enamel*) AND MIH*. After selecting the studies, only three relevant articles published between 1966 and 2011 were included in the review. Conclusion: The presence of several methodological issues does not allow to draw any evidence-based conclusions. No evidence of association was detected, therefore, there is a need of further well-designed studies to assess the scientific evidence of the relationship between amoxicillin and fluorosis and to restrict the prescription of this drug for recurrent upper respiratory tract infections especially acute otitis media (AOM) during the first two years of life. When it is possible can be opportune to use an alternative antibiotic treatment

AUTHOCTHONOUS MICROFLORA IN BIOLOGICAL PRESERVATION OF FOODS: TECHNOLOGICAL CHARACTERIZATION OF STRAINS ISOLATED FROM A PGI PRODUCT OF MARCHE REGION: CIAUSCOLO

The results of an investigation concerning the microbial population of Ciauscolo salami produced in the hinterland of the Marche Region, are reported. Phenotypic assays, namely inhibitory activity against Listeria monocytogenes, acidification ability, proteolysis, and lipolysis were performed. The technological characterization highlighted the presence of a high diversity of autochthonous bacterial population among the 14 producers investigated and a certain number of genetically different strains to be potentially used as starter cultures for the manufacture of Ciauscolo

Adding pieces to the puzzle of differentiated-to-anaplastic thyroid cancer evolution: the oncogene E2F7

Anaplastic Thyroid Cancer (ATC) is the most aggressive and de-differentiated subtype of thyroid cancer. Many studies hypothesized that ATC derives from Differentiated Thyroid Carcinoma (DTC) through a de-differentiation process triggered by specific molecular events still largely unknown. E2F7 is an atypical member of the E2F family. Known as cell cycle inhibitor and keeper of genomic stability, in specific contexts its function is oncogenic, guiding cancer progression. We performed a meta-analysis on 279 gene expression profiles, from 8 Gene Expression Omnibus patient samples datasets, to explore the causal relationship between DTC and ATC. We defined 3 specific gene signatures describing the evolution from normal thyroid tissue to DTC and ATC and validated them in a cohort of human surgically resected ATCs collected in our Institution. We identified E2F7 as a key player in the DTC-ATC transition and showed in vitro that its down-regulation reduced ATC cells’ aggressiveness features. RNA-seq and ChIP-seq profiling allowed the identification of the E2F7 specific gene program, which is mainly related to cell cycle progression and DNA repair ability. Overall, this study identified a signature describing DTC de-differentiation toward ATC subtype and unveiled an E2F7-dependent transcriptional program supporting this process

AUTOANTICORPI E NEUROPATIE

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The novel lncRNA BlackMamba controls the neoplastic phenotype of ALK- anaplastic large cell lymphoma by regulating the DNA helicase HELLS.

The molecular mechanisms leading to the transformation of anaplastic lymphoma kinase negative (ALK-) anaplastic large cell lymphoma (ALCL) have been only in part elucidated. To identify new culprits which promote and drive ALCL, we performed a total transcriptome sequencing and discovered 1208 previously unknown intergenic long noncoding RNAs (lncRNAs), including 18 lncRNAs preferentially expressed in ALCL. We selected an unknown lncRNA, BlackMamba, with an ALK- ALCL preferential expression, for molecular and functional studies. BlackMamba is a chromatin-associated lncRNA regulated by STAT3 via a canonical transcriptional signaling pathway. Knockdown experiments demonstrated that BlackMamba contributes to the pathogenesis of ALCL regulating cell growth and cell morphology. Mechanistically, BlackMamba interacts with the DNA helicase HELLS controlling its recruitment to the promoter regions of cell-architecture-related genes, fostering their expression. Collectively, these findings provide evidence of a previously unknown tumorigenic role of STAT3 via a lncRNA-DNA helicase axis and reveal an undiscovered role for lncRNA in the maintenance of the neoplastic phenotype of ALK-ALCL

Immune-related pan-cancer gene expression signatures of patient survival revealed by NanoString-based analyses

The immune system plays a central role in the onset and progression of cancer. A better understanding of transcriptional changes in immune cell-related genes associated with cancer progression, and their significance in disease prognosis, is therefore needed. NanoString-based targeted gene expression profiling has advantages for deployment in a clinical setting over RNA-seq technologies. We analysed NanoString PanCancer Immune Profiling panel gene expression data encompassing 770 genes, and overall survival data, from multiple previous studies covering 10 different cancer types, including solid and blood malignancies, across 515 patients. This analysis revealed an immune gene signature comprising 39 genes that were upregulated in those patients with shorter overall survival; of these 39 genes, three (MAGEC2, SSX1 and ULBP2) were common to both solid and blood malignancies. Most of the genes identified have previously been reported as relevant in one or more cancer types. Using Cibersort, we investigated immune cell levels within individual cancer types and across groups of cancers, as well as in shorter and longer overall survival groups. Patients with shorter survival had a higher proportion of M2 macrophages and γδ T cells. Patients with longer overall survival had a higher proportion of CD8+ T cells, CD4+ T memory cells, NK cells and, unexpectedly, T regulatory cells. Using a transcriptomics platform with certain advantages for deployment in a clinical setting, our multi-cancer meta-analysis of immune gene expression and overall survival data has identified a specific transcriptional profile associated with poor overall survival