2,279 research outputs found
PhonItalia: a phonological lexicon for Italian.
In this article, we present the first open-access lexical database that provides phonological representations for 120,000 Italian word forms. Each of these also includes syllable boundaries and stress markings and a comprehensive range of lexical statistics. Using data derived from this lexicon, we have also generated a set of derived databases and provided estimates of positional frequency use for Italian phonemes, syllables, syllable onsets and codas, and character and phoneme bigrams. These databases are freely available from phonitalia.org. This article describes the methods, content, and summarizing statistics for these databases. In a first application of this database, we also demonstrate how the distribution of phonological substitution errors made by Italian aphasic patients is related to phoneme frequency
Multitasking associative networks
We introduce a bipartite, diluted and frustrated, network as a sparse
restricted Boltzman machine and we show its thermodynamical equivalence to an
associative working memory able to retrieve multiple patterns in parallel
without falling into spurious states typical of classical neural networks. We
focus on systems processing in parallel a finite (up to logarithmic growth in
the volume) amount of patterns, mirroring the low-level storage of standard
Amit-Gutfreund-Sompolinsky theory. Results obtained trough statistical
mechanics, signal-to-noise technique and Monte Carlo simulations are overall in
perfect agreement and carry interesting biological insights. Indeed, these
associative networks pave new perspectives in the understanding of multitasking
features expressed by complex systems, e.g. neural and immune networks.Comment: to appear on Phys.Rev.Let
Kilo-instruction processors: overcoming the memory wall
Historically, advances in integrated circuit technology have driven improvements in processor microarchitecture and led to todays microprocessors with sophisticated pipelines operating at very high clock frequencies. However, performance improvements achievable by high-frequency microprocessors have become seriously limited by main-memory access latencies because main-memory speeds have improved at a much slower pace than microprocessor speeds. Its crucial to deal with this performance disparity, commonly known as the memory wall, to enable future high-frequency microprocessors to achieve their performance potential. To overcome the memory wall, we propose kilo-instruction processors-superscalar processors that can maintain a thousand or more simultaneous in-flight instructions. Doing so means designing key hardware structures so that the processor can satisfy the high resource requirements without significantly decreasing processor efficiency or increasing energy consumption.Peer ReviewedPostprint (published version
Autophagy in major human diseases
Autophagy is a core molecular pathway for the preservation of cellular and organismal homeostasis. Pharmacological and genetic interventions impairing autophagy responses promote or aggravate disease in a plethora of experimental models. Consistently, mutations in autophagy-related processes cause severe human pathologies. Here, we review and discuss preclinical data linking autophagy dysfunction to the pathogenesis of major human disorders including cancer as well as cardiovascular, neurodegenerative, metabolic, pulmonary, renal, infectious, musculoskeletal, and ocular disorders
Evaluation of Smell and miRNA Biomarkers in Alzheimer’s Disease (AD)
Abstract and poster under embargo until May 31, 2019
An automated fluorescence videomicroscopy assay for the detection of mitotic catastrophe
Mitotic catastrophe can be defined as a cell death mode that occurs during or shortly after a prolonged/aberrant mitosis, and can show apoptotic or necrotic features. However, conventional procedures for the detection of apoptosis or necrosis, including biochemical bulk assays and cytofluorometric techniques, cannot discriminate among pre-mitotic, mitotic and post-mitotic death, and hence are inappropriate to monitor mitotic catastrophe. To address this issue, we generated isogenic human colon carcinoma cell lines that differ in ploidy and p53 status, yet express similar amounts of fluorescent biosensors that allow for the visualization of chromatin (histone H2B coupled to green fluorescent protein (GFP)) and centrosomes (centrin coupled to the Discosoma striata red fluorescent protein (DsRed)). By combining high-resolution fluorescence videomicroscopy and automated image analysis, we established protocols and settings for the simultaneous assessment of ploidy, mitosis, centrosome number and cell death (which in our model system occurs mainly by apoptosis). Time-lapse videomicroscopy showed that this approach can be used for the high-throughput detection of mitotic catastrophe induced by three mechanistically distinct anti-mitotic agents (dimethylenastron (DIMEN), nocodazole (NDZ) and paclitaxel (PTX)), and – in this context – revealed an important role of p53 in the control of centrosome number
Parallel processing in immune networks
In this work we adopt a statistical mechanics approach to investigate basic,
systemic features exhibited by adaptive immune systems. The lymphocyte network
made by B-cells and T-cells is modeled by a bipartite spin-glass, where,
following biological prescriptions, links connecting B-cells and T-cells are
sparse. Interestingly, the dilution performed on links is shown to make the
system able to orchestrate parallel strategies to fight several pathogens at
the same time; this multitasking capability constitutes a remarkable, key
property of immune systems as multiple antigens are always present within the
host. We also define the stochastic process ruling the temporal evolution of
lymphocyte activity, and show its relaxation toward an equilibrium measure
allowing statistical mechanics investigations. Analytical results are compared
with Monte Carlo simulations and signal-to-noise outcomes showing overall
excellent agreement. Finally, within our model, a rationale for the
experimentally well-evidenced correlation between lymphocytosis and
autoimmunity is achieved; this sheds further light on the systemic features
exhibited by immune networks.Comment: 21 pages, 9 figures; to appear in Phys. Rev.
Trial Watch: experimental TLR7/TLR8 agonists for oncological indications
Resiquimod (R848) and motolimod (VTX-2337) are second-generation experimental derivatives of imiquimod, an imidazoquinoline with immunostimulatory properties originally approved by the US Food and Drug Administration for the topical treatment of actinic keratosis and genital warts more than 20 years ago. Both resiquimod and motolimod operate as agonists of Toll-like receptor 7 (TLR7) and/or TLR8, in thus far delivering adjuvant-like signals to antigen-presenting cells (APCs). In line with such an activity, these compounds are currently investigated as immunostimulatory agents for the treatment of various malignancies, especially in combination with peptide-based, dendritic cell-based, cancer cell lysate-based, or DNA-based vaccines. Here, we summarize preclinical and clinical evidence recently collected to support the development of resiquimod and motolimod and other TLR7/TLR8 agonists as anticancer agents
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