Estimation of continuous-time interest rate models: a nonparametric approach

This paper presents a general, nonlinear model for term structure interest rate. The approach is the same of Stanton (1997) but it has been extended to a multifactor model. The novel aspect is that rather than choosing the functional specification of the model, the process is generated from the data using approximation methods for multifactor continuous-time Markov processes. In applying this technique to the short and long end of the term structure for a general two-factor diffusion process for interest rates is possible to find some interesting nonlinearity in the interest rate data that are not considered in almost all parametric specifications of term structure interest rate model of the financial literature.continuous-time models, nonparametric estimation, multi-factor interest rate model

Nonparametric estimation of diffusion process: a closer look

A Monte Carlo simulation is performed to investigate the finite sample properties of a nonparametric estimator, based on discretely sampled observations of continuous-time Ito diffusion process. Chapman and Pearson (2000) studies finite-sample properties of the nonparametric estimator of Aýt-Sahalia (1996) and Stanton (1997) and they find that nonlinearity of the short rate drift is not a robust stylized fact but it’s an artifacts of the estimation procedure. This paper examine the finite sample properties of a different nonparametric estimator within the Stanton (1997)’s framework.ewp-mac/050417

Training Program at Medical School of Chieti, Italy

We describe the changes in medical training program offered at the G. D’Annunzio University Medical School in Chieti-Pescara, Italy, which took place over the last decade. The new curriculum differs from the previous one in several important aspects, including limited number of students admitted to school depending on the estimated needs for physicians, obligatory class attendance, student attendance in preclinical laboratories, formative credits as a measure of student activity, and elective subjects. Furthermore, all medical graduates are allowed to take the State exam to obtain the license to practice, which was not the case previously. As a result of these major changes, a higher number of students graduates in due time. The changes made in the medical education curriculum in Italy have enabled Italian medical graduates to work in European Community Hospitals, because their medical degree is recognized in other EU countries. The main motif that drives the Medical School in Chieti-Pescara is the achievement of high quality in medical education and biomedical research by creating as strong a relationship between education and research as possible

Generation and characterization of genetically encoded fluorescent probes to visualize mitochondria-endoplasmic reticulum contact sites.

openEndoplasmic reticulum (ER) physically contacts mitochondria via its specialized subdomain called mitochondria-associated membranes (MAMs) at sites of mitochondria-ER contacts (MERCs). Interaction between these organelles at the MERCs plays essential roles in lipid and calcium transfer and ultimately in the homeostasis of the two individual organelles. Since the width of the MERCs could be as narrow as 10 nm, which is below the diffraction limit, a handful of probes have been developed to evaluate MERCs formation and dynamics. However, the current probes are dim, or artificially induce tethering, or require complicated imaging procedures that are not compatible with the common imaging setups available to most of the labs. To circumvent these problems, we are developing “STACCATO”, a new generation of probes to visualize MERCs that are based on split Fluorescence-Activating and absorption-Shifting Tag (FAST). STACCATO capitalizes on the reversible nature of split FAST complementation so the probe itself does not work as an artificial tether. In this Thesis we report the generation of a STACCATO probe for MERCs and its initial characterization and we show that STACCATO can report areas of proximity between mitochondria and the endoplasmic reticulum.Endoplasmic reticulum (ER) physically contacts mitochondria via its specialized subdomain called mitochondria-associated membranes (MAMs) at sites of mitochondria-ER contacts (MERCs). Interaction between these organelles at the MERCs plays essential roles in lipid and calcium transfer and ultimately in the homeostasis of the two individual organelles. Since the width of the MERCs could be as narrow as 10 nm, which is below the diffraction limit, a handful of probes have been developed to evaluate MERCs formation and dynamics. However, the current probes are dim, or artificially induce tethering, or require complicated imaging procedures that are not compatible with the common imaging setups available to most of the labs. To circumvent these problems, we are developing “STACCATO”, a new generation of probes to visualize MERCs that are based on split Fluorescence-Activating and absorption-Shifting Tag (FAST). STACCATO capitalizes on the reversible nature of split FAST complementation so the probe itself does not work as an artificial tether. In this Thesis we report the generation of a STACCATO probe for MERCs and its initial characterization and we show that STACCATO can report areas of proximity between mitochondria and the endoplasmic reticulum

Generation of Functional CLL-Specific Cord Blood CTL Using CD40-Ligated CLL APC

PMCID: PMC3526610This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

A pro-inflammatory signalome is constitutively activated by C33Y mutant TNF receptor 1 in TNF receptor-associated periodic syndrome (TRAPS)

Mutations in TNFRSF1A encoding TNF receptor 1 (TNFR1) cause the autosomal dominant TNF receptor-associated periodic syndrome (TRAPS): a systemic autoinflammatory disorder. Misfolding, intracellular aggregation, and ligand-independent signaling by mutant TNFR1 are central to disease pathophysiology. Our aim was to understand the extent of signaling pathway perturbation in TRAPS. A prototypic mutant TNFR1 (C33Y), and wild-type TNFR1 (WT), were expressed at near physiological levels in an SK-Hep-1 cell model. TNFR1-associated signaling pathway intermediates were examined in this model, and in PBMCs from C33Y TRAPS patients and healthy controls. In C33Y-TNFR1-expressing SK-Hep-1 cells and TRAPS patients' PBMCs, a subtle, constitutive upregulation of a wide spectrum of signaling intermediates and their phosphorylated forms was observed; these were associated with a proinflammatory/antiapoptotic phenotype. In TRAPS patients' PBMCs, this upregulation of proinflammatory signaling pathways was observed irrespective of concurrent treatment with glucocorticoids, anakinra or etanercept, and the absence of overt clinical symptoms at the time that the blood samples were taken. This study reveals the pleiotropic effect of a TRAPS-associated mutant form of TNFR1 on inflammatory signaling pathways (a proinflammatory signalome), which is consistent with the variable and limited efficacy of cytokine-blocking therapies in TRAPS. It highlights new potential target pathways for therapeutic intervention

Extracellular Vesicles Involvement in the Modulation of the Glioblastoma Environment

Glioblastoma (GBM) is the most deadly primary brain tumour and is a paradigmatic example of heterogeneous cancer. Although expanding data propose the phenotypic plasticity exhibited by glioblastoma cells, as a critical feature involved in the tumour development and posttherapy recurrence, the central machinery responsible for their aggressiveness remains elusive. Despite decades of research, the complex biology of the glioblastoma is still unknown. Progress in genetic and epigenetic discoveries has improved diagnostic classification, prognostic information, and therapeutic planning. In the complex model of intercellular signalling, several studies have shown that extracellular vesicles have a key role in the intercellular communication among GBM cells and the tumour microenvironment modulation. The purpose of this review is to summarize the role of the EV-mediated intercellular crosstalk in the glioblastoma physiopathology

The Link Among Neurological Diseases: Extracellular Vesicles as a Possible Brain Injury Footprint

Extracellular vesicles (EVs), referred as membranous vesicles released into body fluids from all cell types, represent a novel model to explain some aspects of the inter-cellular cross talk. It has been demonstrated that the EVs modify the phenotype of target cells, acting through a large spectrum of mechanisms. In the central nervous system, the EVs are responsible of the wide range of physiological processes required for normal brain function and neuronal support, such as immune signaling, cellular proliferation, differentiation, and senescence. Growing evidences link the EV functions to the pathogenic machinery of the neurological diseases, contributing to the disease progression and spreading. Extracellular vesicles are involved in the brain injury by multimodal ways; they propagate inflammation across the blood brain barrier (BBB), mediate neuroprotection and modulate regenerative processes. For these reasons, extracellular vesicles represent a promising biomarker in neurological disorders as well as an interesting starting point for the development of novel therapeutic strategies. Herein, we review the role of the EVs in the pathogenesis of neurological disease, discussing their potential clinical applications

Subumbilical versus transumbilical laparoscopic assisted appendectomy in children: a caregivers-centered cosmetic satisfaction evaluation

BaCKgrOuND: Studies suggest that trans-umbilical incisions (Tui) incur better postoperative cosmetic satisfaction scores (CSS) than subumbilical incisions (Sui) but a higher incidence of surgical site infection (SSi). We aimed to compare these outcomes after Tui or Sui for uncomplicated pediatric appendicitis (ua). METhODS: analysis of medical records of 99 children treated at our institution for ua with Tui or Sui. Caregivers underwent a telephonic interview on postoperative course, filling in the Patient Subscale of the Patient and Observer Surgical Assessment Scale (POSAS) version 2.0 – POSaS v. 2.0. rESuLTS: Of 99 eligible patients, 67 participated to the study (12 Sui and 55 Tui). groups were similar for age, sex, BMi, histology of the appendix, incidence of granuloma. Compared to Sui group, Tui group presented shorter operative time (min 87.5±51.41 Sui; 69.43±22.07 Tui. P=0.059), postoperative hospitalization (days, 3.3±1.1 vs. 4±1.84), lower rate of SSi (2/55 vs. 2/12) and lower POSaS Score (11.32±7.65 vs. 14.25±9.2), even if statistically insignificant. A positive overall opinion in both groups was reported (TUI vs. Sui: 2.13±2 vs. 2.5±2, respectively, P=ns). CONCLuSiONS: Tui seems to be preferable over Sui as approach for ua, but larger prospective series are needed to validate these results