Long-Term Outcome After Adoptive Immunotherapy With Natural Killer Cells: Alloreactive NK Cell Dose Still Matters

open26noRecently, many reports were published supporting the clinical use of adoptively transferred natural killer (NK) cells as a therapeutic tool against cancer, including acute myeloid leukemia (AML). Our group demonstrated promising clinical response using adoptive immunotherapy with donor-derived alloreactive KIR-ligand-mismatched NK cells in AML patients. Moreover, the antileukemic effect was correlated with the dose of infused alloreactive NK cells (“functional NK cell dose”). Herein, we update the results of our previous study on a cohort of adult AML patients (median age at enrollment 64) in first morphological complete remission (CR), not eligible for allogeneic stem cell transplantation. After an extended median follow-up of 55.5 months, 8/16 evaluable patients (50%) are still off-therapy and alive disease-free. Overall survival (OS) and disease-free survival (DFS) are related with the dose of infused alloreactive NK cells (≥2 × 105/kg).openParisi S.; Ruggeri L.; Dan E.; Rizzi S.; Sinigaglia B.; Ocadlikova D.; Bontadini A.; Giudice V.; Urbani E.; Ciardelli S.; Sartor C.; Cristiano G.; Nanni J.; Zannoni L.; Chirumbolo G.; Arpinati M.; Lewis R.E.; Bonifazi F.; Marconi G.; Martinelli G.; Papayannidis C.; Paolini S.; Velardi A.; Cavo M.; Lemoli R.M.; Curti A.Parisi, S.; Ruggeri, L.; Dan, E.; Rizzi, S.; Sinigaglia, B.; Ocadlikova, D.; Bontadini, A.; Giudice, V.; Urbani, E.; Ciardelli, S.; Sartor, C.; Cristiano, G.; Nanni, J.; Zannoni, L.; Chirumbolo, G.; Arpinati, M.; Lewis, R. E.; Bonifazi, F.; Marconi, G.; Martinelli, G.; Papayannidis, C.; Paolini, S.; Velardi, A.; Cavo, M.; Lemoli, R. M.; Curti, A

A Parameterised Hierarchy of Argumentation Semantics for Extended Logic Programming and its Application to the Well-founded Semantics

Argumentation has proved a useful tool in defining formal semantics for assumption-based reasoning by viewing a proof as a process in which proponents and opponents attack each others arguments by undercuts (attack to an argument's premise) and rebuts (attack to an argument's conclusion). In this paper, we formulate a variety of notions of attack for extended logic programs from combinations of undercuts and rebuts and define a general hierarchy of argumentation semantics parameterised by the notions of attack chosen by proponent and opponent. We prove the equivalence and subset relationships between the semantics and examine some essential properties concerning consistency and the coherence principle, which relates default negation and explicit negation. Most significantly, we place existing semantics put forward in the literature in our hierarchy and identify a particular argumentation semantics for which we prove equivalence to the paraconsistent well-founded semantics with explicit negation, WFSX$_p$. Finally, we present a general proof theory, based on dialogue trees, and show that it is sound and complete with respect to the argumentation semantics.Comment: To appear in Theory and Practice of Logic Programmin

Modular Logic Argumentation in Arg-tuProlog

A modular extension of Arg-tuProlog, a light-weight argumentation tool, is here presented and discussed, highlighting how it enables reasoning with rules and interpretations of multiple legal systems. Its effectiveness is demonstrated with examples from different national private international law (PIL) laws, running in Arg-tuProlog. PIL addresses overlaps and conflicts between legal systems by distributing cases between the authorities of such systems (jurisdiction) and establishing what rules these authorities have to apply to each case (choice of law)

Dispersive spherical optical model of neutron scattering from Al27 up to 250 MeV

A spherical optical model potential (OMP) containing a dispersive term is used to fit the available experimental database of angular distribution and total cross section data for n + Al27 covering the energy range 0.1- 250 MeV using relativistic kinematics and a relativistic extension of the Schroedinger equation. A dispersive OMP with parameters that show a smooth energy dependence and energy independent geometry are determined from fits to the entire data set. A very good overall agreement between experimental data and predictions is achieved up to 150 MeV. Inclusion of nonlocality effects in the absorptive volume potential allows to achieve an excellent agreement up to 250 MeV.Comment: 13 figures (11 eps and 2 jpg), 3 table

Identification of the expressome by machine learning on omics data.

Accurate annotation of plant genomes remains complex due to the presence of many pseudogenes arising from whole-genome duplication-generated redundancy or the capture and movement of gene fragments by transposable elements. Machine learning on genome-wide epigenetic marks, informed by transcriptomic and proteomic training data, could be used to improve annotations through classification of all putative protein-coding genes as either constitutively silent or able to be expressed. Expressed genes were subclassified as able to express both mRNAs and proteins or only RNAs, and CG gene body methylation was associated only with the former subclass. More than 60,000 protein-coding genes have been annotated in the reference genome of maize inbred B73. About two-thirds of these genes are transcribed and are designated the filtered gene set (FGS). Classification of genes by our trained random forest algorithm was accurate and relied only on histone modifications or DNA methylation patterns within the gene body; promoter methylation was unimportant. Other inbred lines are known to transcribe significantly different sets of genes, indicating that the FGS is specific to B73. We accurately classified the sets of transcribed genes in additional inbred lines, arising from inbred-specific DNA methylation patterns. This approach highlights the potential of using chromatin information to improve annotations of functional genes