Finite size corrections to random Boolean networks

Since their introduction, Boolean networks have been traditionally studied in view of their rich dynamical behavior under different update protocols and for their qualitative analogy with cell regulatory networks. More recently, tools borrowed from statistical physics of disordered systems and from computer science have provided a more complete characterization of their equilibrium behavior. However, the largest part of the results have been obtained in the thermodynamic limit, which is often far from being reached when dealing with realistic instances of the problem. The numerical analysis presented here aims at comparing - for a specific family of models - the outcomes given by the heuristic belief propagation algorithm with those given by exhaustive enumeration. In the second part of the paper some analytical considerations on the validity of the annealed approximation are discussed.Comment: Minor correction

Long-term treatment with high-dose of sildenafil in a thalassemic patient with pulmonary hypertension

We report a case of a 37-years-old man, affected by thalassemia major, hypogonadotropic hypogonadism, chronic HCV-hepatitis, diabetes mellitus, severe osteoporosis, prior septic pulmonary embolism and pulmonary artery hypertension was performed a long-term treatment with highdose of sildenafil (120 mg/die) with reduction of pulmonary arterial systolic pressure and of the dyspnea

Computational core and fixed-point organisation in Boolean networks

In this paper, we analyse large random Boolean networks in terms of a constraint satisfaction problem. We first develop an algorithmic scheme which allows to prune simple logical cascades and under-determined variables, returning thereby the computational core of the network. Second we apply the cavity method to analyse number and organisation of fixed points. We find in particular a phase transition between an easy and a complex regulatory phase, the latter one being characterised by the existence of an exponential number of macroscopically separated fixed-point clusters. The different techniques developed are reinterpreted as algorithms for the analysis of single Boolean networks, and they are applied to analysis and in silico experiments on the gene-regulatory networks of baker's yeast (saccaromices cerevisiae) and the segment-polarity genes of the fruit-fly drosophila melanogaster.Comment: 29 pages, 18 figures, version accepted for publication in JSTA

A parathyroid-hormone-related-protein (PTH-rP)-specific cytotoxic T cell response induced by in vitro stimulation of tumour-infiltrating lymphocytes derived from prostate cancer metastases, with epitope peptide-loaded autologous dendritic cells and low-dose IL-2

Bone metastases are one of the most common events in patients with prostate carcinoma. PTH-rP, a protein produced by prostate carcinoma and other epithelial cancers, is a key agent for the development of bone metastases. A PTH-rP-derived peptide, designated PTR-4 was identified, which is capable to bind HLA-A2.1 molecules and to generate PTH-rP-specific cytotoxic T cell (CTL) lines from healthy HLA-A2.1+ individual peripheral-blood-mononuclear-cells (PBMC). In this model, we investigated the in vitro possibility of generating an efficient PTH-rP specific CTL response by cyclical stimulations with IL-2 and PTR-4 peptide-pulsed autologous dendritic cells (DC), of HLA-A2.1+ tumour infiltrating lymphocytes (TIL) derived from a patient with metastatic prostate carcinoma. A T cell line generated in this way (called TM-PTR-4) had a CD3+, CD5+, CD4−, CD8+, CD45Ro+, CD56− immunophenotype and a HLA-A2.1 restricted cytotoxic activity to PTR-4-peptide pulsed CIR-A2 (HLA-A2.1+) target cells, PTH-rP+/HLA-A2.1+ CIR-A2 transfected with PTH-rP gene, prostate carcinoma LNCaP cells, and autologous metastatic prostate cancer cells (M-CaP). These lymphocytes were not cytotoxic to HLA-A2.1+ targets not producing PTH-rP, such as peptide-unpulsed CIR-A2 and colon carcinoma SW-1463, cell lines. Our results provide evidence that PTR-4 peptide-pulsed autologous DC may break the tolerance of human TIL against the autologous tumour by inducing a PTH-rP-specific CTL immune reaction. In conclusion PTR-4 peptide-pulsed autologous DC may be a promising approach for vaccine-therapy and antigen-specific CTL adoptive immunotherapy of hormone-resistant prostrate cancer. © 2001 Cancer Research Campaign http://www.bjcancer.co

Feasibility of stereotactic ablative reirradiation in breast cancer patient undergoing palbociclib: a case report

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P2613Initial combination therapy with ambrisentan and tadalafil for pulmonary arterial hypertension: clinical effect and haemodynamic changes. A multicenter retrospective analysis

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In vivo study of the GC90/IRIV vaccine for immune response and autoimmunity into a novel humanised transgenic mouse

Parathyroid hormone-related protein (PTH-rP), a secreted protein produced by prostate carcinoma and other epithelial cancers, is considered a key agent for the development of bone metastases. We investigated the construct GC90/IRIV, composed of immunopotentiating reconstituted influenza virosomes (IRIV) containing PTH-rP gene plasmids (GC90), as a potential tool for human anticancer immunotherapy into humanised mice transgenic for HLA-A(*)02.01, the human-β2 microglobulin, and the human CD8α molecule. Intranasal administration of GC90/IRIV resulted in the induction of a PTH-rP-specific multiepitope cytotoxic T-cell (CTL) response. Cytotoxic T cells derived from vaccinated mice were capable of lysing in vitro syngenic murine PTH-rP transfectants and human HLA-A(*)02.01+/PTH-rP+ prostate carcinoma LNCaP cells as well. The immune response capacity and the absence of any sign of toxicity and/or autoimmunity in vivo suggest the GC90/IRIV vaccine as a valid tool for active specific immunotherapy of human cancers and metastases overexpressing PTH-rP

Influence of Heart Rate on Left and Right Ventricular Longitudinal Strain in Patients with Chronic Heart Failure

Over the past years, a number of studies have demonstrated the relevance of strain assessed by two-dimensional speckle tracking echocardiography (STE) in evaluating ventricular function. The aim of this study was to analyze changes in left (LV) and right ventricular (RV) longitudinal strain associated with variations of heart rate (HR) in participants with and without chronic heart failure (CHF). We enrolled 45 patients, 38 of these diagnosed with CHF and carrying an implantable cardioverter defibrillator, and seven patients with pacemakers and without CHF. The frequency of atrial stimulation was increased to 90 beats/min and an echocardiogram was performed at each increase of 10 beats/min. Global LV and RV longitudinal strain (LVGLS and RVGLS, respectively) and RV free wall longitudinal strain (RVfwLS) were calculated at each HR. When analyzed as continuous variables, significant reductions in LVGLS were detected at higher HRs, whereas improvements in both RVGLS and RVfwLS were observed. Patients with a worsening of LVGLS (76% overall) were more likely to present lower baseline LV function. Only a few patients (18% for RVGLS and 16% for RVfwLS) exhibited HR-related deteriorations of RV strain measures, which was associated with lower levels of baseline RV function and higher pulmonary systolic pressures. Finally, 21 (47%) and 25 (56%) participants responded with improvements in RVGLS and RVfwLS, respectively. Our findings revealed heterogeneous RV and LV responses to increases in HR. These findings might ultimately be used to optimize cardiac functionality in patients diagnosed with CHF

Torus knots and mirror symmetry

We propose a spectral curve describing torus knots and links in the B-model. In particular, the application of the topological recursion to this curve generates all their colored HOMFLY invariants. The curve is obtained by exploiting the full Sl(2, Z) symmetry of the spectral curve of the resolved conifold, and should be regarded as the mirror of the topological D-brane associated to torus knots in the large N Gopakumar-Vafa duality. Moreover, we derive the curve as the large N limit of the matrix model computing torus knot invariants.Comment: 30 pages + appendix, 3 figure

Long-Term Remission Achieved by Ponatinib and Donor Lymphocytes Infusion in a Ph+ Acute Lymphoblastic Leukemia Patient in Molecular Relapse After Allogenic Stem Cell Transplant and Dasatinib: A Case Report

Currently, the prognosis of Ph+ acute lymphoblastic leukemia (Ph+ ALL) patients relapsing after an allogenic hematopoietic stem cell transplantation (allo-SCT) remains poor, with few therapeutic options available. Here we present the case of a 32 years old patient with dasatinib-resistant post-transplant molecular relapse of ALL, who received, as second-line therapy, the combination of ponatinib and donor lymphocyte infusion (DLI). The therapy was safe and the patient achieved a sustained minimal residual disease negative disease, still ongoing after 22 months, which was accompanied by several changes in the immune populations distribution within the bone marrow (i.e., the increase in the CD8/CD4 lymphocytes ratio). Our report provides evidence of the efficacy of the third generation TKI inhibitor ponatinib in combination with DLI as second line therapy for Ph+ ALL relapsing after an allo-SCT