Expressiveness and complexity of graph logic

We investigate the complexity and expressive power of the spatial logic for querying graphs introduced by Cardelli, Gardner and Ghelli (ICALP 2002).We show that the model-checking complexity of versions of this logic with and without recursion is PSPACE-complete. In terms of expressive power, the version without recursion is a fragment of the monadic second-order logic of graphs and we show that it can express complete problems at every level of the polynomial hierarchy. We also show that it can define all regular languages, when interpretation is restricted to strings. The expressive power of the logic with recursion is much greater as it can express properties that are PSPACE-complete and therefore unlikely to be definable in second-order logic

Regular Expression Subtyping for XML Query and Update Languages

XML database query languages such as XQuery employ regular expression types with structural subtyping. Subtyping systems typically have two presentations, which should be equivalent: a declarative version in which the subsumption rule may be used anywhere, and an algorithmic version in which the use of subsumption is limited in order to make typechecking syntax-directed and decidable. However, the XQuery standard type system circumvents this issue by using imprecise typing rules for iteration constructs and defining only algorithmic typechecking, and another extant proposal provides more precise types for iteration constructs but ignores subtyping. In this paper, we consider a core XQuery-like language with a subsumption rule and prove the completeness of algorithmic typechecking; this is straightforward for XQuery proper but requires some care in the presence of more precise iteration typing disciplines. We extend this result to an XML update language we have introduced in earlier work.Comment: ESOP 2008. Companion technical report with proof

The cell cycle checkpoint inhibitors in the treatment of leukemias

open3noThe study was funded by the University of Bologna and by the Italian Association for Cancer Research (AIRC).The inhibition of the DNA damage response (DDR) pathway in the treatment of cancers has recently reached an exciting stage with several cell cycle checkpoint inhibitors that are now being tested in several clinical trials in cancer patients. Although the great amount of pre-clinical and clinical data are from the solid tumor experience, only few studies have been done on leukemias using specific cell cycle checkpoint inhibitors. This review aims to summarize the most recent data found on the biological mechanisms of the response to DNA damages highlighting the role of the different elements of the DDR pathway in normal and cancer cells and focusing on the main genetic alteration or aberrant gene expression that has been found on acute and chronic leukemias. This review, for the first time, outlines the most important pre-clinical and clinical data available on the efficacy of cell cycle checkpoint inhibitors in single agent and in combination with different agents normally used for the treatment of acute and chronic leukemias.openGhelli Luserna di Rora', A; Iacobucci, I; Martinelli, GGhelli Luserna di Rora', A; Iacobucci, I; Martinelli,

CDC20 in and out of mitosis: a prognostic factor and therapeutic target in hematological malignancies

Cell division cycle 20 homologue (CDC20) is a well-known regulator of cell cycle, as it controls the correct segregation of chromosomes during mitosis. Many studies have focused on the biological role of CDC20 in cancer development, as alterations of its functionality have been linked to genomic instability and evidence demonstrated that high CDC20 expression levels are associated with poor overall survival in solid cancers. More recently, novel CDC20 functions have been demonstrated or suggested, including the regulation of apoptosis and stemness properties and a correlation with immune cell infiltration. Here, we here summarize and discuss the role of CDC20 inside and outside mitosis, starting from its network of interacting proteins. In the last years, CDC20 has also attracted more interest in the blood cancer field, being overexpressed and showing an association with prognosis both in myeloid and lymphoid malignancies. Preclinical findings showed that selective CDC20 and APC/CCDC20/APC/CCDH1 inhibitors, namely Apcin and proTAME, are effective against lymphoma and multiple myeloma cells, resulting in mitotic arrest and apoptosis and synergizing with clinically-relevant drugs. The evidence and hypothesis presented in this review provide the input for further biological and chemical studies aiming to dissect novel potential CDC20 roles and targeting strategies in hematological malignancies

The formation of SCEs as an effect of occupational exposure to formaldehyde

Formaldehyde (FA) is a ubiquitous toxic chemical employed worldwide due to its disinfectant and preservative properties. Despite being classified as a human carcinogen, FA is still employed as formalin in pathology wards as standard fixative. We evaluated its relationship with the formation of sister-chromatid exchanges (SCEs) in cultured peripheral blood lymphocytes on 57 pathologists and 48 controls and the risk/protective role played by several genetic polymorphisms. All subjects were assessed for SCEs and genotyped for the most common cancer-associated gene polymorphisms: CYP1A1 exon 7 (A > G), CYP1A1*2A (T > C), CYP2C19*2 (G > A), GSTT1 (presence/absence), GSTM1 (presence/absence), GSTP1 (A > G), XRCC1 (G399A), XRCC1 (C194T), XRCC1 (A280G), XPC exon 15 (A939C), XPC exon 9 (C499T), TNFα − 308 G > A), IL10 − 1082 (G > A), and IL6 − 174 (G > C). Air-FA concentration was assessed through passive personal samplers. Pathologists, exposed to 55.2 μg/m(3) of air-FA, showed a significantly higher SCEs frequency than controls, exposed, respectively, to 18.4 μg/m(3). Air-FA was directly correlated with SCEs frequency and inversely with the replication index (RI). Regression models showed FA exposure as a significant predictor in developing SCEs, while did not highlight any role of the selected polymorphisms. Our study confirms the role of low air-FA levels as genotoxicity inductor, highlighting the importance to define exposure limits that could be safer for exposed workers. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00204-022-03238-w