No more conflicts: the development of a generic airport model in a sequence-optimization framework

International audienceComponents of the airport airside such as runways, taxiways and aprons, have a significant impact in the total capacity of the airport system, where capacity is usually considered as maximum number of air traffic movements or number of passengers accommodated in a given period of time. Operations on the airside impact in the propagation of delay and consequently in the perceived level of service by passengers the terminal buildings. This paper put the focus on the airside operations at airports. A methodology for modelling operations on the ground and the successive optimization is proposed. The methodology presented in this paper is generic enough in the sense that it can be applied to any airport. The objective of this work is to come up with a generic tool that can be used by air traffic controllers in order to minimize conflicts on the ground and consequently increase the airport capacit

PNGS: an API Ecosystem for Astronomical Applications Development

PNGS (Pandora Next Generation Software) is a collection of object oriented Application Programming Interfaces (APIs) implementing a broad set of functionalities and routines aimed at the manipulation of spectroscopic astronomical data. In particular a subset of GUI-oriented APIs are available. Based on the FASE (see Grosböl et al. (2012)) framework, PNGS offers a fully customizable software ecosystem which allows to develop applications spanning the whole spectroscopic data life cycle, from data classification to its organization on disk, analysis, reduction, visualization and archiving

Easylife: a Conceptual Framework for Semi-automatic Survey Management

Easylife is a conceptual framework aimed at the semi-automatic management of spectroscopic surveys. Conceived in 2012 (Garilli et al. 2012) as a tool to manage the VIPERS spectroscopic survey (Guzzo et al. 2014) and based on a prototype version of the FASE framework (Grosböl et al. 2012), it evolved into a survey-independent generalised framework following the MVC (Model-View-Controller) paradigm. Easylife has been deeply modified to exploit PNGS (Pandora Next Generation Software) APIs (Fumana et al. 2019) and FASE stable version, and is currently used to manage the ongoing VANDELS ESO public spectroscopic survey carried out using the VIMOS@VLT spectrograph

Validation study of a new chemiluminescent singleplex IgE assay in a set of Italian allergic rhinitis patients

Background: The measurement of specific IgE to allergenic extracts and molecules in patients with allergic rhinitis (AR) is crucial for a precise diagnosis and further immunotherapy. Companies providing in vitro diagnostic methods in allergology continuously strive for the optimization and modernization of such methods. A new generation of automated allergy tests based on chemiluminescence detection and paramagnetic microparticles is now available, with possible advantages in sample volume, cost-effectiveness and avoidance of sample-related interference. Objectives: To test whether sIgE antibody levels obtained with a new singleplex chemiluminescent method have a good agreement with the corresponding results obtained with a "gold standard" test. Methods: We tested sera from 368 AR patients. Specific IgE sera levels (kU/L) to a comprehensive panel of 15 allergen extracts and 6 molecules were tested with ImmunoCAP® (Thermo Fisher Scientific Inc, Phadia AB, Uppsala, Sweden) and NOVEOS™ (HYCOR® Biomedical, Garden Grove, CA, USA). We evaluated the qualitative and quantitative performance of the new NOVEOS system in matching the outcome of ImmunoCAP to each of the examined allergens. Results: In relation to ImmunoCAP, the overall diagnostic sensitivity and specificity of sIgE tests with NOVEOS were 90.8% (95% CI = 88.6-92.7) and 96.2% (95% CI = 93.9-97.8), respectively. These values were higher when only molecules were considered (sensitivity = 98.7% [95% CI = 96.4%-99.7%]; specificity = 94.2% [95% CI = 88.4%-97.6%]) and lower when only extracts were considered (sensitivity = 87.6% [95% CI = 84.7%-90.2%]; specificity = 97% [95% CI = 94.4%-98.6%]). Spearman's correlation between the data set of both methods for a ≥ 0.1 kU/L cut-off was 0.84 (p < .001). Conclusions: The new singleplex NOVEOS system presented good results for qualitative and quantitative comparisons when testing specific serum IgE antibodies against a range of 21 allergens. This novel immunoassay system using only 4 µl of sample per test appears to be robust and reliable and can, therefore, be used as an aid in allergy diagnosis

Cancer-associated CD43 glycoforms as target of immunotherapy

CD43 is a sialoglycosylated membrane protein that is involved in cell proliferation and differentiation. CD43 glycoforms that are recognized by the UN1 monoclonal antibody (mAb) were expressed in lymphoblastoid T-cell lines and solid tumors, such as breast, colon, gastric, and squamous cell lung carcinomas, while unexpressed in the normal counterparts. The cancer association of UN1/CD43 epitope suggested the possibility to use the UN1 mAb for tumor diagnosis and therapy. In this study, we show that the UN1 mAb was endowed with antitumor activity in vivo because its passive transfer inhibited the growth of UN1-positive HPB-ALL lymphoblastoid T cells in mice. Furthermore, we demonstrate that tumor inhibition was due to UN1 mAb-dependent natural killer-mediated cytotoxicity. By screening a phage-displayed random peptide library, we identified the phagotope 2/165 as a mimotope of the UN1 antigen, as it harbored a peptide sequence that was specifically recognized by the UN1 mAb and inhibited the binding of the UN1 mAb to UN1-positive tumor cells. On the basis of sequence homology with the extracellular region of CD43 (amino acids 64 to 83), the 2/165 peptide sequence was likely mimicking the protein core of the UN1/CD43 epitope. When used as vaccine in mice, the 2/165 phagotope raised antibodies against the UN1/CD43 antigen, indicating that the 2/165 phagotope mimicked the UN1 antigen structure, and could represent a novel immunogen for cancer immunotherapy. These findings support the feasibility of using monoclonal antibodies to identify cancer-associated mimotopes for immunotherapy

COX-2 expression positively correlates with PD-L1 expression in human melanoma cells.

Abstract BACKGROUND: The resistance to PD-1/PD-L1 inhibitors for the treatment of melanoma have prompted investigators to implement novel clinical trials which combine immunotherapy with different treatment modalities. Moreover is also important to investigate the mechanisms which regulate the dynamic expression of PD-L1 on tumor cells and PD-1 on T cells in order to identify predictive biomarkers of response. COX-2 is currently investigated as a major player of tumor progression in several type of malignancies including melanoma. In the present study we investigated the potential relationship between COX-2 and PD-L1 expression in melanoma. METHODS: Tumor samples obtained from primary melanoma lesions and not matched lymph node metastases were analyzed for both PD-L1 and COX-2 expression by IHC analysis. Status of BRAF and NRAS mutations was analyzed by sequencing and PCR. Co-localization of PD-L1 and COX-2 expression was analyzed by double fluorescence staining. Lastly the BRAFV600E A375 and NRASQ61R SK-MEL-2 melanoma cell lines were used to evaluate the effect of COX-2 inhibition by celecoxib on expression of PD-L1 in vitro. RESULTS: BRAFV600E/V600K and NRASQ61R/Q61L were detected in 57.8 and 8.9% of the metastatic lesions, and in 65.9 and 6.8% of the primary tumors, respectively. PD-L1 and COX-2 expression were heterogeneously expressed in both primary melanoma lesions and not matched lymph node metastases. A significantly lower number of PD-L1 negative lesions was found in primary tumors as compared to not matched metastatic lesions (P = 0.002). COX-2 expression significantly correlated with PD-L1 expression in both primary (P = 0.001) and not matched metastatic (P = 0.048) lesions. Furthermore, in melanoma tumors, cancer cells expressing a higher levels of COX-2 also co-expressed a higher level of PD-L1. Lastly, inhibition of COX-2 activity by celecoxib down-regulated the expression of PD-L1 in both BRAFV600E A375 and NRASQ61R SK-MEL-2 melanoma cell lines. CONCLUSIONS: COX-2 expression correlates with and modulates PD-L1 expression in melanoma cells. These findings have clinical relevance since they provide a rationale to implement novel clinical trials to test COX-2 inhibition as a potential treatment to prevent melanoma progression and immune evasion as well as to enhance the anti-tumor activity of PD-1/PD-L1 based immunotherapy for the treatment of melanoma patients with or without BRAF/NRAS mutations

Evolution in endoscopic endonasal approach for the management of hypothalamic–pituitary region metastasis: A single-institution experience

IntroductionEndonasal endoscopic surgery has changed the treatment perspectives for different lesions of the hypothalamic–pituitary region. The metastases of the hypothalamic–pituitary region represent 0.4% of all intracranial metastatic tumors and account for only 1.8% of surgically managed pituitary lesions. The aim of tshis study is to describe a single-center institutional experience with 13 cases of hypothalamic–pituitary metastasis focused on presurgical workup, the evolution of the surgical technique, and postsurgical management according to our protocols, showing effects on progression-free and overall survival rates for this relatively uncommon location.Material and MethodsWe retrospectively reviewed the whole series of patients that received the endoscopic endonasal approach at the Division of Neurosurgery at the University of Naples “Federico II” undergoing surgery from January 1997 to December 2021. We identified 13 cases whose pathology reports revealed a metastatic lesion. Statistical analysis was performed to determine the Kaplan–Meier survival function and assess for log-rank differences in survival based on gender, surgical treatment, and postoperative therapy (p-value &lt; 0.02*).ResultsThe pathology report disclosed lung adenocarcinoma (six cases, 46%), breast adenocarcinoma (two cases, 15.4%), clear cell renal carcinoma (one case, 7%), melanoma (one case, 7%), colorectal adenocarcinoma (one case, 7%), uterine cervix carcinoma (one case, 7%), and follicular thyroid carcinoma (one case, 7%). A standard endoscopic endonasal approach was performed in 10 patients (76.9%), while an extended endonasal procedure was performed in only three cases (23%). Biopsy was the surgical choice in five patients with infiltrative and invasive lesions and a poor performance status (38%), while in the cases where neurovascular decompression was necessary, a subtotal resection was achieved in five patients (38%) and partial resection in three patients (23%). Recovery of visual field defect was observed in six of seven patients with visual loss (85.7%), improvement of oculomotor nerve palsy occurred in four of seven patients with this defect (57.1%), while the impairment of oculomotor palsy was observed in three patients (42.9%). Visual function was stable in the other patients. The median progression-free survival and overall survival were 14 and 18 months, respectively. There were statistically significant differences in PFS and OS in patients who underwent adjuvant radiotherapy (p=0.019 is referred to OS and p=0.017 to PFS, respectively; p-value = 0.02).ConclusionsThe endoscopic endonasal approach is a viable approach for the management of hypothalamic–pituitary metastases as this surgery provides an adequate opportunity to obtain tissue sample and neurovascular decompression, both being crucial for continuing the integrated adjuvant therapy protocols

New CXCR4 Antagonist Peptide R (Pep R) Improves Standard Therapy in Colorectal Cancer

he chemokine receptor CXCR4 is overexpressed and functional in colorectal cancer. To investigate the role of CXCR4 antagonism in potentiating colon cancer standard therapy, the new peptide CXCR4 antagonist Peptide R (Pep R) was employed. Human colon cancer HCT116 xenograft-bearing mice were treated with chemotherapeutic agents (CT) 5-Fluorouracil (5FU) and oxaliplatin (OX) or 5FU and radio chemotherapy (RT-CT) in the presence of Pep R. After two weeks, CT plus Pep R reduced by 4-fold the relative tumor volume (RTV) as compared to 2- and 1.6-fold reductions induced, respectively, by CT and Pep R. In vitro Pep R addition to CT/RT-CT impaired HCT116 cell growth and further reduced HCT116 and HT29 clonal capability. Thus, the hypothesis that Pep R could target the epithelial mesenchyme transition (EMT) process was evaluated. While CT decreased ECAD and increased ZEB-1 and CD90 expression, the addition of Pep R restored the pretreatment expression. In HCT116 and HT29 cells, CT/RT-CT induced a population of CD133+CXCR4+ cells, supposedly a stem-resistant cancer cell population, while Pep R reduced it. Taken together, the results showed that targeting CXCR4 ameliorates the effect of treatment in colon cancer through inhibition of cell growth and reversal of EMT treatment-induced markers, supporting further clinical studies

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European-Union Civil Protection Mechanism, DG-ECHO, Agreement Number: ECHO/SUB/2015/718568/PREV26Published6T. Studi di pericolosità sismica e da maremoto1SR TERREMOTI - Sorveglianza Sismica e Allerta Tsunami2SR TERREMOTI - Gestione delle emergenze sismiche e da maremoto4IT. Banche dat