Interactive Learning-Based Realizability for Heyting Arithmetic with EM1

We apply to the semantics of Arithmetic the idea of ``finite approximation'' used to provide computational interpretations of Herbrand's Theorem, and we interpret classical proofs as constructive proofs (with constructive rules for $\vee, \exists$) over a suitable structure \StructureN for the language of natural numbers and maps of G\"odel's system \SystemT. We introduce a new Realizability semantics we call ``Interactive learning-based Realizability'', for Heyting Arithmetic plus \EM_1 (Excluded middle axiom restricted to $\Sigma^0_1$ formulas). Individuals of \StructureN evolve with time, and realizers may ``interact'' with them, by influencing their evolution. We build our semantics over Avigad's fixed point result, but the same semantics may be defined over different constructive interpretations of classical arithmetic (Berardi and de' Liguoro use continuations). Our notion of realizability extends intuitionistic realizability and differs from it only in the atomic case: we interpret atomic realizers as ``learning agents''

From Frictional to Viscous Behavior: Three Dimensional Imaging and Rheology of Gravitational Suspensions

We probe the three dimensional flow structure and rheology of gravitational (non-density matched) suspensions for a range of driving rates in a split-bottom geometry. We establish that for sufficiently slow flows, the suspension flows as if it were a dry granular medium, and confirm recent theoretical modeling on the rheology of split-bottom flows. For faster driving, the flow behavior is shown to be consistent with the rheological behavior predicted by the recently developed "inertial number approaches for suspension flows.Comment: 5 pages, 4 figures, accepted for Phys. Rev. E. (R

Effect of Slow-Moving Landslides on Churches in the Liguria Region: a Geotechnical Approach

Protecting cultural heritage from water-soil interaction related threats is a current issue and the prediction of the effects induced on buildings by landslides is very challenging. The main difficulties lie in the lack of detailed information about landside movements as well as in the modeling of soil-structure interaction. This paper study the effects of a particular category of slow-moving landslides, namely active rotational and translational slides with movement rates of the order of some mm/year, on buildings of historical and cultural interestsuch as churches. Three case studies located in the Liguria region (Italy) were analyzed by performing FEM and LEM numerical analyses on sections representative of the slope

Cinematic and aesthetic cartographies of subjective mutation

This article exmaines the use of cinema as a mapping of subjective mutation in the work of Deleuze, Gauttari and Berardi. Drawing on Deleuze's distinciton between the reduction of the art-work to the symptom and the idea of art as symptomatology, the article focuses on Berardi's use of cinematic examples, posing the quesiton in each case of to what extent they function as symptomatologies or mere symptoms of cultural and subjective mutations in examples ranging from Bergman's Persona to Van Sant's Elephant to finish on speculations about Fincher's The Social Network as a cirtical engagement with subjective mutation in the 21st Century

Core charge distribution and self assembly of columnar phases: the case of triphenylenes and azatriphenylenes

<p>Abstract</p> <p>Background</p> <p>The relation betweeen the structure of discotic molecules and columnar properties, a crucial point for the realization of new advanced materials, is still largely unknown. A paradigmatic case is that hexa-alkyl-thio substituted triphenylenes present mesogenic behavior while the corresponding azatriphenylenes, similar in shape and chemical structure, but with a different core charge distribution, do not form any liquid crystalline mesophase. This study is aimed at investigating, with the help of computer simulations techniques, the effects on phase behaviour of changes of the charge distribution in the discotic core.</p> <p>Results</p> <p>We described the shape and the pair, dispersive and electrostatic, interactions of hexa alkyl triphenylenes by uniaxial Gay-Berne discs with embedded point charges. Gay-Berne parameters were deduced by fitting the dispersive energies obtained from an atomistic molecular dynamics simulation of a small sample of hexa-octyl-thio triphenylene molecules in columnar phase, while a genetic algorithm was used to get a minimal set of point charges that properly reproduces the ab anitio electrostatic potential. We performed Monte Carlo simulations of three molecular models: the pure Gay-Berne disc, used as a reference, the Gay-Berne disc with hexa-thio triphenylene point charges, the Gay-Berne disc with hexa-thio azatriphenylene point charges. The phase diagram of the pure model evidences a rich polymorphism, with isotropic, columnar and crystalline phases at low pressure, and the appearance of nematic phase at higher pressure.</p> <p>Conclusion</p> <p>We found that the intermolecular electrostatic potential among the cores is fundamental in sta-bilizing/destabilizing columnar phases; in particular the triphenylene charge distribution stabilizes the columnar structure, while the azatriphenylene distribution suppresses its formation in favor of the nematic phase. We believe the present model could be successfully employed as the basis for coarse-grained level simulations of a wider class of triphenylene derivatives.</p

Recording Risk Factors of Physical Abuse in Children Younger Than 36 Months With Bone Fractures: A 12-Years Retrospective Study in an Italian General Hospital Emergency Room

Skeletal fractures (SFs) are very common in pediatrics. In some cases, they are secondary to child abuse. Differentiation of accidental from non-accidental fractures (NAFs) is essential as in abused children risk of further injuries leading to severe clinical problems and death is significant. Main objectives of this study were to evaluate the characteristics of SFs of children ≤3 years of age presenting to the Emergency Room (ER) of a Children's Teaching Hospital over a 12-year period and the attention paid by ER physicians to the identification of the indicators that increase suspicion of NAF and that suggest referring of the patient to the child protection agencies. This is a descriptive, retrospective study of the medical records of all the pediatric patients ≤ 36 months of age admitted to the ER of the Azienda Ospedaliera Santa Maria della Misericordia, University of Perugia, Perugia, Italy, for radiological documented SFs between January 1, 2004, and March 31, 2016. Available information was used to evaluate whether indicators of possible child abuse were documented by the ER staff and whether diagnosis of potential abuse was followed by further screening or referral to child protection agencies. During the study period, 11,136 accesses of the ER by children younger than 36 months were documented, among whom 417 presented long bone or skull fractures. Skull fractures were significantly more common among children &lt;12 months of age (p = 0.001), whereas radius/ulna and humerus fractures were diagnosed significantly more frequently in children 12–36 months of age (p = 0.036 and p = 0.022, respectively). Recorded medical history was considered inadequate in 255 (61.2%) cases with no difference related to patient's age. Our study showed that the majority of charts in case of SFs were found to contain inadequate documentation to explain causes at the heart of the fractures and, therefore, to rule out any inflicted trauma. The development of specific referral guidelines, along with the continuous education and training of health professionals, as well as the preparation of structured medical forms, are essential measures to activate in order to improve the referral of children from the ER to child protection agencies

Multifunctional thiosemicarbazones targeting sigma receptors: in vitro and in vivo antitumor activities in pancreatic cancer models

Purpose: Association of the metal chelating portion of thiosemicarbazone with the cytotoxic activity of sigma-2 receptors appears a promising strategy for the treatment of pancreatic tumors. Here, we developed a novel sigma-2 receptor targeting thiosemicarbazone (FA4) that incorporates a moiety associated with lysosome destabilization and ROS increase in order to design more efficient antitumor agents. Methods: The density of sigma receptors in pancreatic cancer cells was evaluated by flow cytometry. In these cells, cytotoxicity (MTT assay) and activation of ER- and mitochondria-dependent cell death pathways (mRNA expression of GRP78, ATF6, IRE1, PERK; ROS levels by MitoSOX and DCFDA-AM; JC-1 staining) induced by the thiosemicarbazones FA4, MLP44, PS3 and ACthio-1, were evaluated. The expression of autophagic proteins (ATG5, ATG7, ATG12, beclin, p62 and LC3-I) was also studied. In addition, the in vivo effect of FA4 in xenograft models with and without gemcitabine challenge was investigated. Results: We found that FA4 exerted a more potent cytotoxicity than previously studied thiosemicarbazones (MLP44, PS3 and ACthio-1), which were found to display variable effects on the ER or the mitochondria-dependent pro-apoptotic axis. By contrast, FA4 activated pro-apoptotic pathways and decreased autophagy, except in MiaPaCa2 cells, in which autophagic proteins were expressed at lower levels and remained unmodified by FA4. FA4 treatment of PANC-1 xenografted mouse models, poorly responsive to conventional chemotherapy, significantly reduced tumor volumes and increased intratumor apoptosis compared to gemcitabine, with no signs of toxicity. Conclusions: Our data indicate that FA4 exhibits encouraging activity in pancreatic cancer cells unresponsive to gemcitabine. These results warrant further investigation in patient-derived pancreatic cancers, and hold promise for the development of therapies that can more efficiently target the specific characteristics of individual tumor types

Anti-cyclic-citrullinated-protein-antibodies in psoriatic arthritis patients: how autoimmune dysregulation could affect clinical characteristics, retention rate of methotrexate monotherapy and first line biotechnological drug survival. A single center retrospective study

Aim: Occasional findings of anti-cyclic-citrullinated-protein-antibodies (anti-CCP) were rarely observed in psoriatic arthritis (PsA). The aim of our study is to evaluate whether the presence of anti-CCP can determine different clinical subsets and influence methotrexate monotherapy survival, and biotechnological drug retention rate. Methods: We conducted a retrospective study on PsA patients. All patients were required to fulfill the CASPAR criteria for PsA, and to present juxta-articular osteo-proliferative signs at X-ray. The exclusion criteria were age less than 18 years old, satisfaction of rheumatoid arthritis classification criteria, and seropositivity for rheumatoid factor. Clinical characteristics, anti-CCP titer, drug survival and comorbidities information were recorded for each patient. Statistical significance was set at p ⩽ 0.05. Results: Of 407 patients with PsA screened 113 were recruited. Twelve patients were anti-CCP positive. Methotrexate monotherapy survival was shorter in patients with anti-CCP (150 ± 48.3 weeks versus 535.3 ± 65.3 weeks; p = 0.026) [discontinuation risk hazard ratio (HR) = 2.389, 95% confidence interval (CI) 1.043, 5.473; p = 0.039] than those without. Significant shorter survival of first-line biotechnological drugs (b-DMARDs) was observed in the anti-CCP positive group than in that without (102.05 ± 24.4 weeks versus 271.6 ± 41.7 weeks; p = 0.005) with higher discontinuation risk (HR = 3.230, 95% CI 1.299, 8.028; p = 0.012). A significant higher rate of multi-failure (more than second-line b-DMARDs) was found in anti-CCP positive patients than in those without (50% versus 14%, p = 0.035). Conclusion: Anti-CCP in PsA could be suggestive of more severe disease, with worse drug survival of both methotrexate monotherapy and first-line b-DMARDs, and higher chance to be b-DMARDs multi-failure. So, they can be considered for more intensive clinical management of these patients

Screening for Bipolar Disorder Symptoms in Depressed Primary Care Attenders: Comparison between Mood Disorder Questionnaire and Hypomania Checklist (HCL-32)

Objective. To describe the prevalence of patients who screen positive for bipolar disorder (BD) symptoms in primary care comparing two screening instruments: Mood Disorders Questionnaire (MDQ) and Hypomania Checklist (HCL-32). Participants. Adult patients presenting to their primary care practitioners for any cause and reporting current depression symptoms or a depressive episode in the last 6 months. Methods. Subjects completed MDQ and HCL-32, and clinical diagnosis was assessed by a psychiatrist following DSM-IV criteria. Depressive symptoms were evaluated in a subgroup with the Patient Health Questionnaire (PHQ-9). Results. A total of 94 patients were approached to participate and 93 completed the survey. Among these, 8.9% screened positive with MDQ and 43.0% with HCL-32. MDQ positive had more likely features associated with BD: panic disorder and smoking habit (P < .05). The best test accuracy was performed by cut-off 5 for MDQ (sensitivity = .91; specificity = .67) and 15 for HCL-32 (sensitivity = .64; specificity = .57). Higher total score of PHQ-9 was related to higher total scores at the screening tests (P < .001). Conclusion. There is a significant prevalence of bipolar symptoms in primary care depressed patients. MDQ seems to have better accuracy and feasibility than HCL-32, features that fit well in the busy setting of primary care